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Sample records for early drosophila development

  1. Coordinated development of muscles and tendon-like structures: early interactions in the Drosophila leg

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    cedric esoler

    2016-02-01

    Full Text Available The formation of the musculoskeletal system is a remarkable example of tissue assembly. In both vertebrates and invertebrates, precise connectivity between muscles and skeleton (or exoskeleton via tendons or equivalent structures is fundamental for movement and stability of the body. The molecular and cellular processes underpinning muscle formation are well established and significant advances have been made in understanding tendon development. However, the mechanisms contributing to proper connection between these two tissues have received less attention. Observations of coordinated development of tendons and muscles suggest these tissues may interact during the different steps in their development. There is growing evidence that, depending on animal model and muscle type, these interactions can take place from progenitor induction to the final step of the formation of the musculoskeletal system. Here we briefly review and compare the mechanisms behind muscle and tendon interaction throughout the development of vertebrates and Drosophila before going on to discuss our recent findings on the coordinated development of muscles and tendon-like structures in Drosophila leg. By altering apodeme formation (the functional Drosophila equivalent of tendons in vertebrates during the early steps of leg development, we affect the spatial localisation of subsequent myoblasts. These findings provide the first evidence of the developmental impact of early interactions between muscle and tendon-like precursors, and confirm the appendicular Drosophila muscle system as a valuable model for studying these processes.

  2. A core transcriptional network for early mesoderm development in Drosophila melanogaster

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    Sandmann, Thomas; Girardot, Charles; Brehme, Marc; Tongprasit, Waraporn; Stolc, Viktor; Furlong, Eileen E.M.

    2007-01-01

    Embryogenesis is controlled by large gene-regulatory networks, which generate spatially and temporally refined patterns of gene expression. Here, we report the characteristics of the regulatory network orchestrating early mesodermal development in the fruitfly Drosophila, where the transcription factor Twist is both necessary and sufficient to drive development. Through the integration of chromatin immunoprecipitation followed by microarray analysis (ChIP-on-chip) experiments during discrete ...

  3. Early development of Drosophila embryos requires Smc5/6 function during oogenesis.

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    Tran, Martin; Tsarouhas, Vasilios; Kegel, Andreas

    2016-07-15

    Mutations in structural maintenance of chromosomes (Smc) proteins are frequently associated with chromosomal abnormalities commonly observed in developmental disorders. However, the role of Smc proteins in development still remains elusive. To investigate Smc5/6 function during early embryogenesis we examined smc5 and smc6 mutants of the fruit fly Drosophila melanogaster using a combination of reverse genetics and microscopy approaches. Smc5/6 exhibited a maternally contributed function in maintaining chromosome stability during early embryo development, which manifested as female subfertility in its absence. Loss of Smc5/6 caused an arrest and a considerable delay in embryo development accompanied by fragmented nuclei and increased anaphase-bridge formation, respectively. Surprisingly, early embryonic arrest was attributable to the absence of Smc5/6 during oogenesis, which resulted in insufficient repair of pre-meiotic and meiotic DNA double-strand breaks. Thus, our findings contribute to the understanding of Smc proteins in higher eukaryotic development by highlighting a maternal function in chromosome maintenance and a link between oogenesis and early embryogenesis.

  4. Early development of Drosophila embryos requires Smc5/6 function during oogenesis

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    Martin Tran

    2016-07-01

    Full Text Available Mutations in structural maintenance of chromosomes (Smc proteins are frequently associated with chromosomal abnormalities commonly observed in developmental disorders. However, the role of Smc proteins in development still remains elusive. To investigate Smc5/6 function during early embryogenesis we examined smc5 and smc6 mutants of the fruit fly Drosophila melanogaster using a combination of reverse genetics and microscopy approaches. Smc5/6 exhibited a maternally contributed function in maintaining chromosome stability during early embryo development, which manifested as female subfertility in its absence. Loss of Smc5/6 caused an arrest and a considerable delay in embryo development accompanied by fragmented nuclei and increased anaphase-bridge formation, respectively. Surprisingly, early embryonic arrest was attributable to the absence of Smc5/6 during oogenesis, which resulted in insufficient repair of pre-meiotic and meiotic DNA double-strand breaks. Thus, our findings contribute to the understanding of Smc proteins in higher eukaryotic development by highlighting a maternal function in chromosome maintenance and a link between oogenesis and early embryogenesis.

  5. Global gene expression shift during the transition from early neural development to late neuronal differentiation in Drosophila melanogaster.

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    Rafael Cantera

    Full Text Available Regulation of transcription is one of the mechanisms involved in animal development, directing changes in patterning and cell fate specification. Large temporal data series, based on microarrays across the life cycle of the fly Drosophila melanogaster, revealed the existence of groups of genes which expression increases or decreases temporally correlated during the life cycle. These groups of genes are enriched in different biological functions. Here, instead of searching for temporal coincidence in gene expression using the entire genome expression data, we searched for temporal coincidence in gene expression only within predefined catalogues of functionally related genes and investigated whether a catalogue's expression profile can be used to generate larger catalogues, enriched in genes necessary for the same function. We analyzed the expression profiles from genes already associated with early neurodevelopment and late neurodifferentiation, at embryonic stages 16 and 17 of Drosophila life cycle. We hypothesized that during this interval we would find global downregulation of genes important for early neuronal development together with global upregulation of genes necessary for the final differentiation of neurons. Our results were consistent with this hypothesis. We then investigated if the expression profile of gene catalogues representing particular processes of neural development matched the temporal sequence along which these processes occur. The profiles of genes involved in patterning, neurogenesis, axogenesis or synaptic transmission matched the prediction, with largest transcript values at the time when the corresponding biological process takes place in the embryo. Furthermore, we obtained catalogues enriched in genes involved in temporally matching functions by performing a genome-wide systematic search for genes with their highest expression levels at the corresponding embryonic intervals. These findings imply the use of gene

  6. SUMOylation in Drosophila Development

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    Albert J. Courey

    2012-07-01

    Full Text Available Small ubiquitin-related modifier (SUMO, an ~90 amino acid ubiquitin-like protein, is highly conserved throughout the eukaryotic domain. Like ubiquitin, SUMO is covalently attached to lysine side chains in a large number of target proteins. In contrast to ubiquitin, SUMO does not have a direct role in targeting proteins for proteasomal degradation. However, like ubiquitin, SUMO does modulate protein function in a variety of other ways. This includes effects on protein conformation, subcellular localization, and protein–protein interactions. Significant insight into the in vivo role of SUMOylation has been provided by studies in Drosophila that combine genetic manipulation, proteomic, and biochemical analysis. Such studies have revealed that the SUMO conjugation pathway regulates a wide variety of critical cellular and developmental processes, including chromatin/chromosome function, eggshell patterning, embryonic pattern formation, metamorphosis, larval and pupal development, neurogenesis, development of the innate immune system, and apoptosis. This review discusses our current understanding of the diverse roles for SUMO in Drosophila development.

  7. Noncanonical compensation of zygotic X transcription in early Drosophila melanogaster development revealed through single-embryo RNA-seq.

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    Susan E Lott

    Full Text Available When Drosophila melanogaster embryos initiate zygotic transcription around mitotic cycle 10, the dose-sensitive expression of specialized genes on the X chromosome triggers a sex-determination cascade that, among other things, compensates for differences in sex chromosome dose by hypertranscribing the single X chromosome in males. However, there is an approximately 1 hour delay between the onset of zygotic transcription and the establishment of canonical dosage compensation near the end of mitotic cycle 14. During this time, zygotic transcription drives segmentation, cellularization, and other important developmental events. Since many of the genes involved in these processes are on the X chromosome, we wondered whether they are transcribed at higher levels in females and whether this might lead to sex-specific early embryonic patterning. To investigate this possibility, we developed methods to precisely stage, sex, and characterize the transcriptomes of individual embryos. We measured genome-wide mRNA abundance in male and female embryos at eight timepoints, spanning mitotic cycle 10 through late cycle 14, using polymorphisms between parental lines to distinguish maternal and zygotic transcription. We found limited sex-specific zygotic transcription, with a weak tendency for genes on the X to be expressed at higher levels in females. However, transcripts derived from the single X chromosome in males were more abundant that those derived from either X chromosome in females, demonstrating that there is widespread dosage compensation prior to the activation of the canonical MSL-mediated dosage compensation system. Crucially, this new system of early zygotic dosage compensation results in nearly identical transcript levels for key X-linked developmental regulators, including giant (gt, brinker (brk, buttonhead (btd, and short gastrulation (sog, in male and female embryos.

  8. Quantitative models of the mechanisms that control genome-wide patterns of transcription factor binding during early Drosophila development.

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    Tommy Kaplan

    2011-02-01

    Full Text Available Transcription factors that drive complex patterns of gene expression during animal development bind to thousands of genomic regions, with quantitative differences in binding across bound regions mediating their activity. While we now have tools to characterize the DNA affinities of these proteins and to precisely measure their genome-wide distribution in vivo, our understanding of the forces that determine where, when, and to what extent they bind remains primitive. Here we use a thermodynamic model of transcription factor binding to evaluate the contribution of different biophysical forces to the binding of five regulators of early embryonic anterior-posterior patterning in Drosophila melanogaster. Predictions based on DNA sequence and in vitro protein-DNA affinities alone achieve a correlation of ∼0.4 with experimental measurements of in vivo binding. Incorporating cooperativity and competition among the five factors, and accounting for spatial patterning by modeling binding in every nucleus independently, had little effect on prediction accuracy. A major source of error was the prediction of binding events that do not occur in vivo, which we hypothesized reflected reduced accessibility of chromatin. To test this, we incorporated experimental measurements of genome-wide DNA accessibility into our model, effectively restricting predicted binding to regions of open chromatin. This dramatically improved our predictions to a correlation of 0.6-0.9 for various factors across known target genes. Finally, we used our model to quantify the roles of DNA sequence, accessibility, and binding competition and cooperativity. Our results show that, in regions of open chromatin, binding can be predicted almost exclusively by the sequence specificity of individual factors, with a minimal role for protein interactions. We suggest that a combination of experimentally determined chromatin accessibility data and simple computational models of transcription

  9. Early-born neurons in type II neuroblast lineages establish a larval primordium and integrate into adult circuitry during central complex development in Drosophila.

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    Riebli, Nadia; Viktorin, Gudrun; Reichert, Heinrich

    2013-04-23

    The central complex is a multimodal information-processing center in the insect brain composed of thousands of neurons representing more than 50 neural types arranged in a stereotyped modular neuroarchitecture. In Drosophila, the development of the central complex begins in the larval stages when immature structures termed primordia are formed. However, the identity and origin of the neurons that form these primordia and, hence, the fate of these neurons during subsequent metamorphosis and in the adult brain, are unknown. Here, we used two pointed-Gal4 lines to identify the neural cells that form the primordium of the fan-shaped body, a major component of the Drosophila central complex. We found that these early-born primordium neurons are generated by four identified type II neuroblasts that amplify neurogenesis through intermediate progenitors, and we demonstrate that these neurons generate the fan-shaped body primordium during larval development in a highly specific manner. Moreover, we characterize the extensive growth and differentiation that these early-born primordium neurons undergo during metamorphosis in pupal stages and show that these neurons persist in the adult central complex, where they manifest layer-specific innervation of the mature fan-shaped body. Taken together, these findings indicate that early-born neurons from type II neuroblast lineages have dual roles in the development of a complex brain neuropile. During larval stages they contribute to the formation of a specific central complex primordium; during subsequent pupal development they undergo extensive growth and differentiation and integrate into the modular circuitry of the adult brain central complex.

  10. P-TEFb, the super elongation complex and mediator regulate a subset of non-paused genes during early Drosophila embryo development.

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    Olle Dahlberg

    2015-02-01

    Full Text Available Positive Transcription Elongation Factor b (P-TEFb is a kinase consisting of Cdk9 and Cyclin T that releases RNA Polymerase II (Pol II into active elongation. It can assemble into a larger Super Elongation Complex (SEC consisting of additional elongation factors. Here, we use a miRNA-based approach to knock down the maternal contribution of P-TEFb and SEC components in early Drosophila embryos. P-TEFb or SEC depletion results in loss of cells from the embryo posterior and in cellularization defects. Interestingly, the expression of many patterning genes containing promoter-proximal paused Pol II is relatively normal in P-TEFb embryos. Instead, P-TEFb and SEC are required for expression of some non-paused, rapidly transcribed genes in pre-cellular embryos, including the cellularization gene Serendipity-α. We also demonstrate that another P-TEFb regulated gene, terminus, has an essential function in embryo development. Similar morphological and gene expression phenotypes were observed upon knock down of Mediator subunits, providing in vivo evidence that P-TEFb, the SEC and Mediator collaborate in transcription control. Surprisingly, P-TEFb depletion does not affect the ratio of Pol II at the promoter versus the 3' end, despite affecting global Pol II Ser2 phosphorylation levels. Instead, Pol II occupancy is reduced at P-TEFb down-regulated genes. We conclude that a subset of non-paused, pre-cellular genes are among the most susceptible to reduced P-TEFb, SEC and Mediator levels in Drosophila embryos.

  11. Lipid metabolism in Drosophila: development and disease

    Institute of Scientific and Technical Information of China (English)

    Zhonghua Liu; Xun Huang

    2013-01-01

    Proteins,nucleic acids,and lipids are three major components of the cell.Despite a few basic metabolic pathways,we know very little about lipids,compared with the explosion of knowledge about proteins and nucleic acids.How many different forms of lipids are there? What are the in vivo functions of individual lipid? How does lipid metabolism contribute to normal development and human health? Many of these questions remain unanswered.For over a century,the fruit fly Drosophila melanogaster has been used as a model organism to study basic biological questions.In recent years,increasing evidences proved that Drosophila models are highly valuable for lipid metabolism and energy homeostasis researches.Some recent progresses of lipid metabolic regulation during Drosophila development and in Drosophila models of human diseases will be discussed in this review.

  12. Collective synchronization of divisions in Drosophila development

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    Vergassola, Massimo

    Mitoses in the early development of most metazoans are rapid and synchronized across the entire embryo. While diffusion is too slow, in vitro experiments have shown that waves of the cell-cycle regulator Cdk1 can transfer information rapidly across hundreds of microns. However, the signaling dynamics and the physical properties of chemical waves during embryonic development remain unclear. We develop FRET biosensors for the activity of Cdk1 and the checkpoint kinase Chk1 in Drosophila embryos and exploit them to measure waves in vivo. We demonstrate that Cdk1 chemical waves control mitotic waves and that their speed is regulated by the activity of Cdk1 during the S-phase (and not mitosis). We quantify the progressive slowdown of the waves with developmental cycles and identify its underlying control mechanism by the DNA replication checkpoint through the Chk1/Wee1 pathway. The global dynamics of the mitotic signaling network illustrates a novel control principle: the S-phase activity of Cdk1 regulates the speed of the mitotic wave, while the Cdk1 positive feedback ensures an invariantly rapid onset of mitosis. Mathematical modeling captures the speed of the waves and predicts a fundamental distinction between the S-phase Cdk1 trigger waves and the mitotic phase waves, which is illustrated by embryonic ablation experiments. In collaboration with Victoria Deneke1, Anna Melbinger2, and Stefano Di Talia1 1 Department of Cell Biology, Duke University Medical Center 2 Department of Physics, University of California San Diego.

  13. Development of larval motor circuits in Drosophila.

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    Kohsaka, Hiroshi; Okusawa, Satoko; Itakura, Yuki; Fushiki, Akira; Nose, Akinao

    2012-04-01

    How are functional neural circuits formed during development? Despite recent advances in our understanding of the development of individual neurons, little is known about how complex circuits are assembled to generate specific behaviors. Here, we describe the ways in which Drosophila motor circuits serve as an excellent model system to tackle this problem. We first summarize what has been learned during the past decades on the connectivity and development of component neurons, in particular motor neurons and sensory feedback neurons. We then review recent progress in our understanding of the development of the circuits as well as studies that apply optogenetics and other innovative techniques to dissect the circuit diagram. New approaches using Drosophila as a model system are now making it possible to search for developmental rules that regulate the construction of neural circuits.

  14. Transcriptomic Response of Drosophila Melanogaster Pupae Developed in Hypergravity

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    Hosamani, Ravikumar; Hateley, Shannon; Bhardwaj, Shilpa R.; Pachter, Lior; Bhattacharya, Sharmila

    2016-01-01

    The metamorphosis of Drosophila is evolutionarily adapted to Earth's gravity, and is a tightly regulated process. Deviation from 1g to microgravity or hypergravity can influence metamorphosis, and alter associated gene expression. Understanding the relationship between an altered gravity environment and developmental processes is important for NASA's space travel goals. In the present study, 20 female and 20 male synchronized (Canton S, 2 to 3day old) flies were allowed to lay eggs while being maintained in a hypergravity environment (3g). Centrifugation was briefly stopped to discard the parent flies after 24hrs of egg laying, and then immediately continued until the eggs developed into P6-staged pupae (25 - 43 hours after pupation initiation). Post hypergravity exposure, P6-staged pupae were collected, total RNA was extracted using Qiagen RNeasy mini kits. We used RNA-Seq and qRT-PCR techniques to profile global transcriptomic changes in early pupae exposed to chronic hypergravity. During the pupal stage, Drosophila relies upon gravitational cues for proper development. Assessing gene expression changes in the pupa under altered gravity conditions helps highlight gravity dependent genetic pathways. A robust transcriptional response was observed in hypergravity-exposed pupae compared to controls, with 1,513 genes showing a significant (q Drosophila pupae in response to hypergravity.

  15. Evolutionary Techniques for Image Processing a Large Dataset of Early Drosophila Gene Expression

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    David M. Holloway

    2003-07-01

    Full Text Available Understanding how genetic networks act in embryonic development requires a detailed and statistically significant dataset integrating diverse observational results. The fruit fly (Drosophila melanogaster is used as a model organism for studying developmental genetics. In recent years, several laboratories have systematically gathered confocal microscopy images of patterns of activity (expression for genes governing early Drosophila development. Due to both the high variability between fruit fly embryos and diverse sources of observational errors, some new nontrivial procedures for processing and integrating the raw observations are required. Here we describe processing techniques based on genetic algorithms and discuss their efficacy in decreasing observational errors and illuminating the natural variability in gene expression patterns. The specific developmental problem studied is anteroposterior specification of the body plan.

  16. Spatial expression of transcription factors in Drosophila embryonic organ development.

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    Hammonds, Ann S; Bristow, Christopher A; Fisher, William W; Weiszmann, Richard; Wu, Siqi; Hartenstein, Volker; Kellis, Manolis; Yu, Bin; Frise, Erwin; Celniker, Susan E

    2013-12-20

    Site-specific transcription factors (TFs) bind DNA regulatory elements to control expression of target genes, forming the core of gene regulatory networks. Despite decades of research, most studies focus on only a small number of TFs and the roles of many remain unknown. We present a systematic characterization of spatiotemporal gene expression patterns for all known or predicted Drosophila TFs throughout embryogenesis, the first such comprehensive study for any metazoan animal. We generated RNA expression patterns for all 708 TFs by in situ hybridization, annotated the patterns using an anatomical controlled vocabulary, and analyzed TF expression in the context of organ system development. Nearly all TFs are expressed during embryogenesis and more than half are specifically expressed in the central nervous system. Compared to other genes, TFs are enriched early in the development of most organ systems, and throughout the development of the nervous system. Of the 535 TFs with spatially restricted expression, 79% are dynamically expressed in multiple organ systems while 21% show single-organ specificity. Of those expressed in multiple organ systems, 77 TFs are restricted to a single organ system either early or late in development. Expression patterns for 354 TFs are characterized for the first time in this study. We produced a reference TF dataset for the investigation of gene regulatory networks in embryogenesis, and gained insight into the expression dynamics of the full complement of TFs controlling the development of each organ system.

  17. Developing a Drosophila Model of Schwannomatosis

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    2012-08-01

    found to associate with RasV12;scrib–/– tumors and to reduce tumor growth in scrib–/– animals (Pastor- Pareja et al., 2008). The Drosophila genome...2006). Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr. Biol. 16, 1139-1146. Igaki, T., Pastor- Pareja ...genome. Nat. Genet. 36, 288-292. Pastor- Pareja , J. C., Wu, M. and Xu. T. (2008). An innate immune response of blood cells to tumors and tissue damage in

  18. Stable, precise, and reproducible patterning of bicoid and hunchback molecules in the early Drosophila embryo.

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    Yurie Okabe-Oho

    2009-08-01

    Full Text Available Precise patterning of morphogen molecules and their accurate reading out are of key importance in embryonic development. Recent experiments have visualized distributions of proteins in developing embryos and shown that the gradient of concentration of Bicoid morphogen in Drosophila embryos is established rapidly after fertilization and remains stable through syncytial mitoses. This stable Bicoid gradient is read out in a precise way to distribute Hunchback with small fluctuations in each embryo and in a reproducible way, with small embryo-to-embryo fluctuation. The mechanisms of such stable, precise, and reproducible patterning through noisy cellular processes, however, still remain mysterious. To address these issues, here we develop the one- and three-dimensional stochastic models of the early Drosophila embryo. The simulated results show that the fluctuation in expression of the hunchback gene is dominated by the random arrival of Bicoid at the hunchback enhancer. Slow diffusion of Hunchback protein, however, averages out this intense fluctuation, leading to the precise patterning of distribution of Hunchback without loss of sharpness of the boundary of its distribution. The coordinated rates of diffusion and transport of input Bicoid and output Hunchback play decisive roles in suppressing fluctuations arising from the dynamical structure change in embryos and those arising from the random diffusion of molecules, and give rise to the stable, precise, and reproducible patterning of Bicoid and Hunchback distributions.

  19. Nerve-muscle interactions during flight muscle development in Drosophila

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    Fernandes, J. J.; Keshishian, H.

    1998-01-01

    During Drosophila pupal metamorphosis, the motoneurons and muscles differentiate synchronously, providing an opportunity for extensive intercellular regulation during synapse formation. We examined the existence of such interactions by developmentally delaying or permanently eliminating synaptic partners during the formation of indirect flight muscles. When we experimentally delayed muscle development, we found that although adult-specific primary motoneuron branching still occurred, the higher order (synaptic) branching was suspended until the delayed muscle fibers reached a favourable developmental state. In reciprocal experiments we found that denervation caused a decrease in the myoblast pool. Furthermore, the formation of certain muscle fibers (dorsoventral muscles) was specifically blocked. Exceptions were the adult muscles that use larval muscle fibers as myoblast fusion targets (dorsal longitudinal muscles). However, when these muscles were experimentally compelled to develop without their larval precursors, they showed an absolute dependence on the motoneurons for their formation. These data show that the size of the myoblast pool and early events in fiber formation depend on the presence of the nerve, and that, conversely, peripheral arbor development and synaptogenesis is closely synchronized with the developmental state of the muscle.

  20. Modeling transcriptional networks in Drosophila development at multiple scales.

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    Wunderlich, Zeba; DePace, Angela H

    2011-12-01

    Quantitative models of developmental processes can provide insights at multiple scales. Ultimately, models may be particularly informative for key questions about network level behavior during development such as how does the system respond to environmental perturbation, or operate reliably in different genetic backgrounds? The transcriptional networks that pattern the Drosophila embryo have been the subject of numerous quantitative experimental studies coupled to modeling frameworks in recent years. In this review, we describe three studies that consider these networks at different levels of molecular detail and therefore result in different types of insights. We also discuss other developmental transcriptional networks operating in Drosophila, with the goal of highlighting what additional insights they may provide.

  1. NIP/DuoxA is essential for Drosophila embryonic development and regulates oxidative stress response.

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    Xie, Xiaojun; Hu, Jack; Liu, Xiping; Qin, Hanjuan; Percival-Smith, Anthony; Rao, Yong; Li, Shawn S C

    2010-05-11

    NIP/DuoxA, originally cloned as a protein capable of binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS) production in mammalian systems. Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox) enzyme, the in vivo function of NIP/DuoxA has not been characterized to date. Here we report a genetic and functional characterization of nip in Drosophila melanogaster. We show that nip is essential for Drosophila development as nip null mutants die at the 1(st) larval instar. Expression of UAS-nip, but not UAS-Duox, rescued the lethality. To understand the function of nip beyond the early larval stage, we generated GAL4 inducible UAS-RNAi transgenes. da(G32)-GAL4 driven, ubiquitous RNAi-mediated silencing of nip led to profound abnormality in pre-adult development, crinkled wing and markedly reduced lifespan at 29 degrees C. Compared to wild type flies, da-GAL4 induced nip-RNAi transgenic flies exhibited significantly reduced ability to survive under oxidative stress and displayed impaired mitochondrial aconitase function. Our work provides in vivo evidence for a critical role for nip in the development and oxidative stress response in Drosophila.

  2. NIP/DuoxA is essential for Drosophila embryonic development and regulates oxidative stress response

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    Xiaojun Xie, Jack Hu, Xiping Liu, Hanjuan Qin, Anthony Percival-Smith, Yong Rao, Shawn S.C. Li

    2010-01-01

    Full Text Available NIP/DuoxA, originally cloned as a protein capable of binding to the cell fate determinant Numb in Drosophila, was recently identified as a modulator of reactive oxygen species (ROS production in mammalian systems. Despite biochemical and cellular studies that link NIP/DuoxA to the generation of ROS through the dual oxidase (Duox enzyme, the in vivo function of NIP/DuoxA has not been characterized to date. Here we report a genetic and functional characterization of nip in Drosophila melanogaster. We show that nip is essential for Drosophila development as nip null mutants die at the 1st larval instar. Expression of UAS-nip, but not UAS-Duox, rescued the lethality. To understand the function of nip beyond the early larval stage, we generated GAL4 inducible UAS-RNAi transgenes. daG32-GAL4 driven, ubiquitous RNAi-mediated silencing of nip led to profound abnormality in pre-adult development, crinkled wing and markedly reduced lifespan at 29°C. Compared to wild type flies, da-GAL4 induced nip-RNAi transgenic flies exhibited significantly reduced ability to survive under oxidative stress and displayed impaired mitochondrial aconitase function. Our work provides in vivo evidence for a critical role for nip in the development and oxidative stress response in Drosophila.

  3. Xenopus BTBD6 and its Drosophila homologue lute are required for neuronal development.

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    Bury, Frédéric J; Moers, Virginie; Yan, Jiekun; Souopgui, Jacob; Quan, Xiao-Jiang; De Geest, Natalie; Kricha, Sadia; Hassan, Bassem A; Bellefroid, Eric J

    2008-11-01

    BBP proteins constitute a subclass of CUL3 interacting BTB proteins whose in vivo function remains unknown. Here, we show that the Xenopus BBP gene BTBD6 and the single Drosophila homologue of mammalian BBP genes lute are strongly expressed in the developing nervous system. In Xenopus, BTBD6 expression responds positively to proneural and negatively to neurogenic gene overexpression. Knockdown of BTBD6 in Xenopus or loss of Drosophila lute result in embryos with strong defects in late neuronal markers and strongly reduced and disorganized axons while early neural development is unaffected. XBTBD6 knockdown in Xenopus also affects muscle development. Together, these data indicate that BTBD6/lute is required for proper embryogenesis and plays an essential evolutionary conserved role during neuronal development.

  4. The ecdysteroidome of Drosophila: influence of diet and development.

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    Lavrynenko, Oksana; Rodenfels, Jonathan; Carvalho, Maria; Dye, Natalie A; Lafont, Rene; Eaton, Suzanne; Shevchenko, Andrej

    2015-11-01

    Ecdysteroids are the hormones regulating development, physiology and fertility in arthropods, which synthesize them exclusively from dietary sterols. But how dietary sterol diversity influences the ecdysteroid profile, how animals ensure the production of desired hormones and whether there are functional differences between different ecdysteroids produced in vivo remains unknown. This is because currently there is no analytical technology for unbiased, comprehensive and quantitative assessment of the full complement of endogenous ecdysteroids. We developed a new LC-MS/MS method to screen the entire chemical space of ecdysteroid-related structures and to quantify known and newly discovered hormones and their catabolites. We quantified the ecdysteroidome in Drosophila melanogaster and investigated how the ecdysteroid profile varies with diet and development. We show that Drosophila can produce four different classes of ecdysteroids, which are obligatorily derived from four types of dietary sterol precursors. Drosophila makes makisterone A from plant sterols and epi-makisterone A from ergosterol, the major yeast sterol. However, they prefer to selectively utilize scarce ergosterol precursors to make a novel hormone 24,28-dehydromakisterone A and trace cholesterol to synthesize 20-hydroxyecdysone. Interestingly, epi-makisterone A supports only larval development, whereas all other ecdysteroids allow full adult development. We suggest that evolutionary pressure against producing epi-C-24 ecdysteroids might explain selective utilization of ergosterol precursors and the puzzling preference for cholesterol.

  5. Genome-Wide Approaches to Drosophila Heart Development

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    Manfred Frasch

    2016-05-01

    Full Text Available The development of the dorsal vessel in Drosophila is one of the first systems in which key mechanisms regulating cardiogenesis have been defined in great detail at the genetic and molecular level. Due to evolutionary conservation, these findings have also provided major inputs into studies of cardiogenesis in vertebrates. Many of the major components that control Drosophila cardiogenesis were discovered based on candidate gene approaches and their functions were defined by employing the outstanding genetic tools and molecular techniques available in this system. More recently, approaches have been taken that aim to interrogate the entire genome in order to identify novel components and describe genomic features that are pertinent to the regulation of heart development. Apart from classical forward genetic screens, the availability of the thoroughly annotated Drosophila genome sequence made new genome-wide approaches possible, which include the generation of massive numbers of RNA interference (RNAi reagents that were used in forward genetic screens, as well as studies of the transcriptomes and proteomes of the developing heart under normal and experimentally manipulated conditions. Moreover, genome-wide chromatin immunoprecipitation experiments have been performed with the aim to define the full set of genomic binding sites of the major cardiogenic transcription factors, their relevant target genes, and a more complete picture of the regulatory network that drives cardiogenesis. This review will give an overview on these genome-wide approaches to Drosophila heart development and on computational analyses of the obtained information that ultimately aim to provide a description of this process at the systems level.

  6. Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis

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    Pushpavalli Sreerangam NCVL

    2013-01-01

    Full Text Available Abstract Background In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Results Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof1/+; mnkp6/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. Conclusion mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using

  7. Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis.

    Science.gov (United States)

    Pushpavalli, Sreerangam N C V L; Sarkar, Arpita; Ramaiah, M Janaki; Chowdhury, Debabani Roy; Bhadra, Utpal; Pal-Bhadra, Manika

    2013-01-24

    In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof¹/+; mnkp⁶/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using Drosophila as model system and carry out the interaction of MOF

  8. Embryonic development of the insect central complex: insights from lineages in the grasshopper and Drosophila.

    Science.gov (United States)

    Boyan, George; Williams, Leslie

    2011-07-01

    The neurons of the insect brain derive from neuroblasts which delaminate from the neuroectoderm at stereotypic locations during early embryogenesis. In both grasshopper and Drosophila, each developing neuroblast acquires an intrinsic capacity for neuronal proliferation in a cell autonomous manner and generates a specific lineage of neural progeny which is nearly invariant and unique. Maps revealing numbers and distributions of brain neuroblasts now exist for various species, and in both grasshopper and Drosophila four putatively homologous neuroblasts have been identified whose progeny direct axons to the protocerebral bridge and then to the central body via an equivalent set of tracts. Lineage analysis in the grasshopper nervous system reveals that the progeny of a neuroblast maintain their topological position within the lineage throughout embryogenesis. We have taken advantage of this to study the pioneering of the so-called w, x, y, z tracts, to show how fascicle switching generates central body neuroarchitecture, and to evaluate the roles of so-called intermediate progenitors as well as programmed cell death in shaping lineage structure. The novel form of neurogenesis involving intermediate progenitors has been demonstrated in grasshopper, Drosophila and mammalian cortical development and may represent a general strategy for increasing brain size and complexity. An analysis of gap junctional communication involving serotonergic cells reveals an intrinsic cellular organization which may relate to the presence of such transient progenitors in central complex lineages. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Development and characterization of a chemically defined food for Drosophila.

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    Wen-Chih Lee

    Full Text Available Diet can affect a spectrum of biological processes ranging from behavior to cellular metabolism. Yet, the precise role of an individual dietary constituent can be a difficult variable to isolate experimentally. A chemically defined food (CDF permits the systematic evaluation of individual macro- and micronutrients. In addition, CDF facilitates the direct comparison of data obtained independently from different laboratories. Here, we report the development and characterization of a CDF for Drosophila. We show that CDF can support the long-term culture of laboratory strains and demonstrate that this formulation has utility in isolating macronutrient from caloric density requirements in studies of development, longevity and reproduction.

  10. Early events in speciation: polymorphism for hybrid male sterility in Drosophila.

    Science.gov (United States)

    Reed, Laura K; Markow, Therese A

    2004-06-15

    Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an early stage.

  11. A critical period of sleep for development of courtship circuitry and behavior in Drosophila.

    Science.gov (United States)

    Kayser, Matthew S; Yue, Zhifeng; Sehgal, Amita

    2014-04-18

    Most animals sleep more early in life than in adulthood, but the function of early sleep is not known. Using Drosophila, we found that increased sleep in young flies was associated with an elevated arousal threshold and resistance to sleep deprivation. Excess sleep results from decreased inhibition of a sleep-promoting region by a specific dopaminergic circuit. Experimental hyperactivation of this circuit in young flies results in sleep loss and lasting deficits in adult courtship behaviors. These deficits are accompanied by impaired development of a single olfactory glomerulus, VA1v, which normally displays extensive sleep-dependent growth after eclosion. Our results demonstrate that sleep promotes normal brain development that gives rise to an adult behavior critical for species propagation and suggest that rapidly growing regions of the brain are most susceptible to sleep perturbations early in life.

  12. Development of a two photon microscope for tracking Drosophila larvae

    Science.gov (United States)

    Karagyozov, Doycho; Mihovilovic Skanata, Mirna; Gershow, Marc

    Current in vivo methods for measuring neural activity in Drosophila larva require immobilization of the animal. Although we can record neural signals while stimulating the sensory organs, we cannot read the behavioral output because we have prevented the animal from moving. Many research questions cannot be answered without observation of neural activity in behaving (freely-moving) animals. Our project aims to develop a tracking microscope that maintains the neurons of interest in the field of view and in focus during the rapid three dimensional motion of a free larva.

  13. Function and dynamics of slam in furrow formation in early Drosophila embryo.

    Science.gov (United States)

    Acharya, Sreemukta; Laupsien, Philip; Wenzl, Christian; Yan, Shuling; Großhans, Jörg

    2014-02-15

    The Drosophila embryo undergoes a developmental transition in the blastoderm stage switching from syncytial to cellular development. The cleavage furrow, which encloses nuclei into cells, is a prominent morphological feature of this transition. It is not clear how the pattern of the furrow array is defined and how zygotic genes trigger the formation and invagination of interphase furrows. A key to these questions is provided by the gene slam, which has been previously implicated in controlling furrow invagination. Here we investigate the null phenotype of slam, the dynamics of Slam protein, and its control by the recycling endosome. We find that slam is essential for furrow invagination during cellularisation and together with nullo, for specification of the furrow. During cellularisation, Slam marks first the furrow, which is derived from the metaphase furrow of the previous mitosis. Slightly later, Slam accumulates at new furrows between daughter cells early in interphase. Slam is stably associated with the furrow canal except for the onset of cellularisation as revealed by FRAP experiments. Restriction of Slam to the furrow canal and Slam mobility during cellularisation is controlled by the recycling endosome and centrosomes. We propose a three step model. The retracting metaphase furrow leaves an initial mark. This mark and the border between corresponding daughter nuclei are refined by vesicular transport away from pericentrosomal recycling endosome towards the margins of the somatic buds. Following the onset of zygotic gene expression, Slam and Nullo together stabilise this mark and Slam triggers invagination of the cleavage furrow.

  14. Early Developments, 2002.

    Science.gov (United States)

    Winton, Pam, Ed.; Buysse, Virginia, Ed.

    2002-01-01

    This document consists of the three 2002 issues of a journal reporting new research in early child development conducted by the Frank Porter Graham Child Development Center (FPG) at the University of North Carolina at Chapel Hill. Articles in the Winter 2002 issue highlight some current work at FPG on factors that enhance or inhibit social and…

  15. The DOCK protein sponge binds to ELMO and functions in Drosophila embryonic CNS development.

    Directory of Open Access Journals (Sweden)

    Bridget Biersmith

    Full Text Available Cell morphogenesis, which requires rearrangement of the actin cytoskeleton, is essential to coordinate the development of tissues such as the musculature and nervous system during normal embryonic development. One class of signaling proteins that regulate actin cytoskeletal rearrangement is the evolutionarily conserved CDM (C. elegansCed-5, human DOCK180, DrosophilaMyoblast city, or Mbc family of proteins, which function as unconventional guanine nucleotide exchange factors for the small GTPase Rac. This CDM-Rac protein complex is sufficient for Rac activation, but is enhanced upon the association of CDM proteins with the ELMO/Ced-12 family of proteins. We identified and characterized the role of Drosophila Sponge (Spg, the vertebrate DOCK3/DOCK4 counterpart as an ELMO-interacting protein. Our analysis shows Spg mRNA and protein is expressed in the visceral musculature and developing nervous system, suggesting a role for Spg in later embryogenesis. As maternal null mutants of spg die early in development, we utilized genetic interaction analysis to uncover the role of Spg in central nervous system (CNS development. Consistent with its role in ELMO-dependent pathways, we found genetic interactions with spg and elmo mutants exhibited aberrant axonal defects. In addition, our data suggests Ncad may be responsible for recruiting Spg to the membrane, possibly in CNS development. Our findings not only characterize the role of a new DOCK family member, but help to further understand the role of signaling downstream of N-cadherin in neuronal development.

  16. Drosophila provides rapid modeling of renal development, function, and disease.

    Science.gov (United States)

    Dow, Julian A T; Romero, Michael F

    2010-12-01

    The evolution of specialized excretory cells is a cornerstone of the metazoan radiation, and the basic tasks performed by Drosophila and human renal systems are similar. The development of the Drosophila renal (Malpighian) tubule is a classic example of branched tubular morphogenesis, allowing study of mesenchymal-to-epithelial transitions, stem cell-mediated regeneration, and the evolution of a glomerular kidney. Tubule function employs conserved transport proteins, such as the Na(+), K(+)-ATPase and V-ATPase, aquaporins, inward rectifier K(+) channels, and organic solute transporters, regulated by cAMP, cGMP, nitric oxide, and calcium. In addition to generation and selective reabsorption of primary urine, the tubule plays roles in metabolism and excretion of xenobiotics, and in innate immunity. The gene expression resource FlyAtlas.org shows that the tubule is an ideal tissue for the modeling of renal diseases, such as nephrolithiasis and Bartter syndrome, or for inborn errors of metabolism. Studies are assisted by uniquely powerful genetic and transgenic resources, the widespread availability of mutant stocks, and low-cost, rapid deployment of new transgenics to allow manipulation of renal function in an organotypic context.

  17. Drosophila neural stem cells in brain development and tumor formation.

    Science.gov (United States)

    Jiang, Yanrui; Reichert, Heinrich

    2014-01-01

    Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system.

  18. Drosophila Smad2 Opposes Mad Signaling during Wing Vein Development

    Science.gov (United States)

    Sander, Veronika; Eivers, Edward; Choi, Renee H.; De Robertis, Edward M.

    2010-01-01

    In the vertebrates, the BMP/Smad1 and TGF-β/Smad2 signaling pathways execute antagonistic functions in different contexts of development. The differentiation of specific structures results from the balance between these two pathways. For example, the gastrula organizer/node of the vertebrates requires a region of low Smad1 and high Smad2 signaling. In Drosophila, Mad regulates tissue determination and growth in the wing, but the function of dSmad2 in wing patterning is largely unknown. In this study, we used an RNAi loss-of-function approach to investigate dSmad2 signaling during wing development. RNAi-mediated knockdown of dSmad2 caused formation of extra vein tissue, with phenotypes similar to those seen in Dpp/Mad gain-of-function. Clonal analyses revealed that the normal function of dSmad2 is to inhibit the response of wing intervein cells to the extracellular Dpp morphogen gradient that specifies vein formation, as measured by expression of the activated phospho-Mad protein. The effect of dSmad2 depletion in promoting vein differentiation was dependent on Medea, the co-factor shared by Mad and dSmad2. Furthermore, double RNAi experiments showed that Mad is epistatic to dSmad2. In other words, depletion of Smad2 had no effect in Mad-deficient wings. Our results demonstrate a novel role for dSmad2 in opposing Mad-mediated vein formation in the wing. We propose that the main function of dActivin/dSmad2 in Drosophila wing development is to antagonize Dpp/Mad signaling. Possible molecular mechanisms for the opposition between dSmad2 and Mad signaling are discussed. PMID:20442782

  19. Effects of Synthetic Diets Enriched in Specific Nutrients on Drosophila Development, Body Fat, and Lifespan.

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    Tânia Reis

    Full Text Available Gene-diet interactions play a crucial but poorly understood role in susceptibility to obesity. Accordingly, the development of genetically tractable model systems to study the influence of diets in obesity-prone genetic backgrounds is a focus of current research. Here I present a modified synthetic Drosophila diet optimized for timely larval development, a stage dedicated to energy storage. Specifically increasing the levels of individual macronutrients-carbohydrate, lipid, or protein-resulted in markedly different organismal effects. A high-carbohydrate diet adversely affected the timing of development, size, early lifespan and body fat. Strikingly, quadrupling the amount of dietary lipids had none of these effects. Diets rich in protein appeared to be the most beneficial, as larvae developed faster, with no change in size, into long-lived adults. I believe this synthetic diet will significantly facilitate the study of gene-diet interactions in organismal energy balance.

  20. Effects of Synthetic Diets Enriched in Specific Nutrients on Drosophila Development, Body Fat, and Lifespan.

    Science.gov (United States)

    Reis, Tânia

    2016-01-01

    Gene-diet interactions play a crucial but poorly understood role in susceptibility to obesity. Accordingly, the development of genetically tractable model systems to study the influence of diets in obesity-prone genetic backgrounds is a focus of current research. Here I present a modified synthetic Drosophila diet optimized for timely larval development, a stage dedicated to energy storage. Specifically increasing the levels of individual macronutrients-carbohydrate, lipid, or protein-resulted in markedly different organismal effects. A high-carbohydrate diet adversely affected the timing of development, size, early lifespan and body fat. Strikingly, quadrupling the amount of dietary lipids had none of these effects. Diets rich in protein appeared to be the most beneficial, as larvae developed faster, with no change in size, into long-lived adults. I believe this synthetic diet will significantly facilitate the study of gene-diet interactions in organismal energy balance.

  1. Effect of the gene transformer of Anastrepha on the somatic sexual development of Drosophila.

    Science.gov (United States)

    Ruiz, María-Fernanda; Sánchez, Lucas

    2010-01-01

    The gene transformer (tra) is the key regulatory memory device for sex determination in tephritid insects. The present manuscript addressed the question about the functional conservation of the tephritid Anastrepha Transformer protein to direct somatic sexual development in Drosophila (Drosophilidae). The transformer cDNA of Anastrepha encoding the putative full-length Tra protein was cloned in pUAST and introduced into Drosophila melanogaster. To express this protein, the GAL4-UAS system was used. The Anastrepha Tra protein induced the female-specific splicing of both dsx and fru pre-mRNAs in Drosophila XY male flies, so that these became transformed into females, though this transformation was incomplete (the sexually dimorphic foreleg basitarsus and the external terminalia were monitored). It was found that the degree of female transformation directly depended on the dose of Anastrepha tra and Drosophila transformer-2 (tra-2) genes, and that the Anastrepha Tra-Drosophila Tra2 complex is not as efficient as the Drosophila Tra-Tra2 complex at inducing the female-specific splicing of Drosophila dsx pre-mRNA. This can explain why the Anastrepha Tra protein cannot fully substitute for the endogenous Drosophila Tra protein.

  2. MiniCORVET is a Vps8-containing early endosomal tether in Drosophila

    Science.gov (United States)

    Lőrincz, Péter; Lakatos, Zsolt; Varga, Ágnes; Maruzs, Tamás; Simon-Vecsei, Zsófia; Darula, Zsuzsanna; Benkő, Péter; Csordás, Gábor; Lippai, Mónika; Andó, István; Hegedűs, Krisztina; Medzihradszky, Katalin F; Takáts, Szabolcs; Juhász, Gábor

    2016-01-01

    Yeast studies identified two heterohexameric tethering complexes, which consist of 4 shared (Vps11, Vps16, Vps18 and Vps33) and 2 specific subunits: Vps3 and Vps8 (CORVET) versus Vps39 and Vps41 (HOPS). CORVET is an early and HOPS is a late endosomal tether. The function of HOPS is well known in animal cells, while CORVET is poorly characterized. Here we show that Drosophila Vps8 is highly expressed in hemocytes and nephrocytes, and localizes to early endosomes despite the lack of a clear Vps3 homolog. We find that Vps8 forms a complex and acts together with Vps16A, Dor/Vps18 and Car/Vps33A, and loss of any of these proteins leads to fragmentation of endosomes. Surprisingly, Vps11 deletion causes enlargement of endosomes, similar to loss of the HOPS-specific subunits Vps39 and Lt/Vps41. We thus identify a 4 subunit-containing miniCORVET complex as an unconventional early endosomal tether in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.14226.001 PMID:27253064

  3. Development of a Drosophila cell-based error correction assay

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    Jeffrey D. Salemi

    2013-07-01

    Full Text Available Accurate transmission of the genome through cell division requires microtubules from opposing spindle poles to interact with protein super-structures called kinetochores that assemble on each sister chromatid. Most kinetochores establish erroneous attachments that are destabilized through a process called error correction. Failure to correct improper kinetochore-microtubule (kt-MT interactions before anaphase onset results in chromosomal instability (CIN, which has been implicated in tumorigenesis and tumor adaptation. Thus, it is important to characterize the molecular basis of error correction to better comprehend how CIN occurs and how it can be modulated. An error correction assay has been previously developed in cultured mammalian cells in which incorrect kt-MT attachments are created through the induction of monopolar spindle assembly via chemical inhibition of kinesin-5. Error correction is then monitored following inhibitor wash out. Implementing the error correction assay in Drosophila melanogaster S2 cells would be valuable because kt-MT attachments are easily visualized and the cells are highly amenable to RNAi and high-throughput screening. However, Drosophila kinesin-5 (Klp61F is unaffected by available small molecule inhibitors. To overcome this limitation, we have rendered S2 cells susceptible to kinesin-5 inhibitors by functionally replacing Klp61F with human kinesin-5 (Eg5. Eg5 expression rescued the assembly of monopolar spindles typically caused by Klp61F depletion. Eg5-mediated bipoles collapsed into monopoles due to the activity of kinesin-14 (Ncd when treated with the kinesin-5 inhibitor S-trityl-L-cysteine (STLC. Furthermore, bipolar spindles reassembled and error correction was observed after STLC wash out. Importantly, error correction in Eg5-expressing S2 cells was dependent on the well-established error correction kinase Aurora B. This system provides a powerful new cell-based platform for studying error correction and

  4. Development of a Drosophila cell-based error correction assay.

    Science.gov (United States)

    Salemi, Jeffrey D; McGilvray, Philip T; Maresca, Thomas J

    2013-01-01

    Accurate transmission of the genome through cell division requires microtubules from opposing spindle poles to interact with protein super-structures called kinetochores that assemble on each sister chromatid. Most kinetochores establish erroneous attachments that are destabilized through a process called error correction. Failure to correct improper kinetochore-microtubule (kt-MT) interactions before anaphase onset results in chromosomal instability (CIN), which has been implicated in tumorigenesis and tumor adaptation. Thus, it is important to characterize the molecular basis of error correction to better comprehend how CIN occurs and how it can be modulated. An error correction assay has been previously developed in cultured mammalian cells in which incorrect kt-MT attachments are created through the induction of monopolar spindle assembly via chemical inhibition of kinesin-5. Error correction is then monitored following inhibitor wash out. Implementing the error correction assay in Drosophila melanogaster S2 cells would be valuable because kt-MT attachments are easily visualized and the cells are highly amenable to RNAi and high-throughput screening. However, Drosophila kinesin-5 (Klp61F) is unaffected by available small molecule inhibitors. To overcome this limitation, we have rendered S2 cells susceptible to kinesin-5 inhibitors by functionally replacing Klp61F with human kinesin-5 (Eg5). Eg5 expression rescued the assembly of monopolar spindles typically caused by Klp61F depletion. Eg5-mediated bipoles collapsed into monopoles due, in part, to kinesin-14 (Ncd) activity when treated with the kinesin-5 inhibitor S-trityl-L-cysteine (STLC). Furthermore, bipolar spindles reassembled and error correction was observed after STLC wash out. Importantly, error correction in Eg5-expressing S2 cells was dependent on the well-established error correction kinase Aurora B. This system provides a powerful new cell-based platform for studying error correction and CIN.

  5. Expression of Drosophila forkhead transcription factors during kidney development.

    Science.gov (United States)

    Baek, Jeong-In; Choi, Soo Young; Chacon-Heszele, Maria F; Zuo, Xiaofeng; Lipschutz, Joshua H

    2014-03-28

    The Drosophila forkhead (Dfkh) family of transcription factors has over 40 family members. One Dfkh family member, BF2 (aka FoxD1), has been shown, by targeted disruption, to be essential for kidney development. In order to determine if other Dfkh family members were involved in kidney development and to search for new members of this family, reverse transcriptase polymerase chain reaction (RT-PCR) was performed using degenerate primers of the consensus sequence of the DNA binding domain of this family and developing rat kidney RNA. The RT-PCR product was used to probe RNA from a developing rat kidney (neonatal), from a 20-day old kidney, and from an adult kidney. The RT-PCR product hybridized only to a developing kidney RNA transcript of ∼2.3 kb (the size of BF2). A lambda gt10 mouse neonatal kidney library was then screened, using the above-described RT-PCR product as a probe. Three lambda phage clones were isolated that strongly hybridized to the RT-PCR probe. Sequencing of the RT-PCR product and the lambda phage clones isolated from the developing kidney library revealed Dfkh BF2. In summary, only Dfkh family member BF2, which has already been shown to be essential for nephrogenesis, was identified in our screen and no other candidate Dfkh family members were identified.

  6. The development of adult abdominal muscles in Drosophila: myoblasts express twist and are associated with nerves.

    Science.gov (United States)

    Currie, D A; Bate, M

    1991-09-01

    During metamorphosis, the adult muscles of the Drosophila abdomen develop from pools of myoblasts that are present in the larva. The adult myoblasts express twist in the third larval instar and the early pupa and are closely associated with nerves. Growing adult nerves and the twist-expressing cells migrate out across the developing abdominal epidermis, and as twist expression declines, the myoblasts begin to synthesize beta 3 tubulin. There follows a process involving cell fusion and segregation into cell groups to form multinucleate muscle precursors. These bipolar precursors migrate at both ends to find their correct attachment points. beta 3 tubulin expression continues at least until 51 h APF by which time the adult muscle pattern has been established.

  7. twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development.

    Science.gov (United States)

    Czerny, T; Halder, G; Kloter, U; Souabni, A; Gehring, W J; Busslinger, M

    1999-03-01

    The Drosophila Pax-6 gene eyeless (ey) plays a key role in eye development. Here we show tht Drosophila contains a second Pax-6 gene, twin of eyeless (toy), due to a duplication during insect evolution. Toy is more similar to vertebrate Pax-6 proteins than Ey with regard to overall sequence conservation, DNA-binding function, and early expression in the embryo, toy and ey share a similar expression pattern in the developing visual system, and targeted expression of Toy, like Ey, induces the formation of ectopic eyes. Genetic and biochemical evidence indicates, however, that Toy functions upstream of ey by directly regulating the eye-specific enhancer of ey. Toy is therefore required for initiation of ey expression in the embryo and acts through Ey to activate the eye developmental program.

  8. Centralspindlin is required for thorax development during Drosophila metamorphosis.

    Science.gov (United States)

    Sfregola, Michael

    2014-05-01

    Epithelial morphogenesis is an essential process in all metazoans during both normal development and pathological processes such as wound healing. The coordinated regulation of cell shape, cell size, and cell adhesion during the migration of epithelial sheets ultimately gives rise to the diversity of body plans among different organisms as well as the diversity of cellular structures and tissues within an organism. Metamorphosis of the Drosophila pupa is an excellent system to study these transformative events. During pupal development, the cells of the wing imaginal discs migrate dorsally and fuse to form the adult thorax. Here I show centralspindlin, a protein complex well known for its role in cytokinesis, is essential for migration of wing disc cells and proper thorax closure. I show the subcellular localization of centralspindlin is important for its function in thorax development. This study demonstrates the emerging role of centralspindlin in regulating cell migration and cell adhesion in addition to its previously known function during cytokinesis. © 2014 Wiley Periodicals, Inc.

  9. Chromosomal distribution of PcG proteins during Drosophila development.

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    Nicolas Nègre

    2006-06-01

    Full Text Available Polycomb group (PcG proteins are able to maintain the memory of silent transcriptional states of homeotic genes throughout development. In Drosophila, they form multimeric complexes that bind to specific DNA regulatory elements named PcG response elements (PREs. To date, few PREs have been identified and the chromosomal distribution of PcG proteins during development is unknown. We used chromatin immunoprecipitation (ChIP with genomic tiling path microarrays to analyze the binding profile of the PcG proteins Polycomb (PC and Polyhomeotic (PH across 10 Mb of euchromatin. We also analyzed the distribution of GAGA factor (GAF, a sequence-specific DNA binding protein that is found at most previously identified PREs. Our data show that PC and PH often bind to clustered regions within large loci that encode transcription factors which play multiple roles in developmental patterning and in the regulation of cell proliferation. GAF co-localizes with PC and PH to a limited extent, suggesting that GAF is not a necessary component of chromatin at PREs. Finally, the chromosome-association profile of PC and PH changes during development, suggesting that the function of these proteins in the regulation of some of their target genes might be more dynamic than previously anticipated.

  10. Small Peptides as Newcomers in the Control of Drosophila Development.

    Science.gov (United States)

    Zanet, J; Chanut-Delalande, H; Plaza, Serge; Payre, Francios

    2016-01-01

    Throughout the last century, studies using the fruit fly have contributed to the discovery of many key genetic elements that control animal development. Recent work has shed light on an unexpectedly large number of RNAs that lack the classical hallmarks of protein-coding genes and are thus referred to as noncoding RNAs. However, there is mounting evidence that both mRNA and noncoding RNAs often contain small open reading frames (sORFs/smORFs), which can be translated into peptides. While genome-wide profiling supports a pervasive translation of these noncanonical sORF/smORF/SEP peptides, their functions remain poorly understood. Here, we review recent data obtained in Drosophila demonstrating the overlooked role of smORF peptides in the control of development and adult life. Focusing on a few smORF peptides whose functions have been elucidated recently, we discuss the importance of these newly identified regulatory molecules and how they act to regulate the building and function of the whole organism.

  11. Role of elongator subunit Elp3 in Drosophila melanogaster larval development and immunity

    DEFF Research Database (Denmark)

    Walker, Jane; Kwon, So Yeon; Badenhorst, Paul

    2011-01-01

    The Elongator complex has been implicated in several cellular processes, including gene expression and tRNA modification. We investigated the biological importance of the Elp3 gene in Drosophila melanogaster. Deletion of Elp3 results in larval lethality at the pupal stage. During early development......, larval growth is dramatically impaired, with progression to the third instar delayed for ~24 hr, and pupariation occurring only at day 14 after egg laying. Melanotic nodules appear after 4 days. Microarray analysis shows that stress response genes are induced and ecdysone-induced transcription factors...... are severely repressed in the mutant. Interestingly, the phenotypes of Elp3 flies are similar to those of flies lacking the domino gene, encoding a SWI/SNF-like ATP-dependent chromatin-remodeling enzyme. Indeed, the gene expression profiles of these mutants are also remarkably similar. Together, these data...

  12. Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.

    Directory of Open Access Journals (Sweden)

    Sokol V Todi

    Full Text Available BACKGROUND: Myosin VIIA (MyoVIIA is an unconventional myosin necessary for vertebrate audition [1]-[5]. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization [6]. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck, are semi-lethal [7] and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO organization [8]. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase. Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.

  13. The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo

    Science.gov (United States)

    Halfon, M. S.; Keshishian, H.

    1998-01-01

    The Toll signaling pathway functions in several Drosophila processes, including dorsal-ventral pattern formation and the immune response. Here, we demonstrate that this pathway is required in the epidermis for proper muscle development. Previously, we showed that the zygotic Toll protein is necessary for normal muscle development; in the absence of zygotic Toll, close to 50% of hemisegments have muscle patterning defects consisting of missing, duplicated and misinserted muscle fibers (Halfon, M.S., Hashimoto, C., and Keshishian, H., Dev. Biol. 169, 151-167, 1995). We have now also analyzed the requirements for easter, spatzle, tube, and pelle, all of which function in the Toll-mediated dorsal-ventral patterning pathway. We find that spatzle, tube, and pelle, but not easter, are necessary for muscle development. Mutations in these genes give a phenotype identical to that seen in Toll mutants, suggesting that elements of the same pathway used for Toll signaling in dorsal-ventral development are used during muscle development. By expressing the Toll cDNA under the control of distinct Toll enhancer elements in Toll mutant flies, we have examined the spatial requirements for Toll expression during muscle development. Expression of Toll in a subset of epidermal cells that includes the epidermal muscle attachment cells, but not Toll expression in the musculature, is necessary for proper muscle development. Our results suggest that signals received by the epidermis early during muscle development are an important part of the muscle patterning process.

  14. Identification of Novel Regulators of atonal Expression in the Developing Drosophila Retina

    Science.gov (United States)

    Melicharek, David; Shah, Arpit; DiStefano, Ginnene; Gangemi, Andrew J.; Orapallo, Andrew; Vrailas-Mortimer, Alysia D.; Marenda, Daniel R.

    2008-01-01

    Atonal is a Drosophila proneural protein required for the proper formation of the R8 photoreceptor cell, the founding photoreceptor cell in the developing retina. Proper expression and refinement of the Atonal protein is essential for the proper formation of the Drosophila adult eye. In vertebrates, expression of transcription factors orthologous to Drosophila Atonal (MATH5/Atoh7, XATH5, and ATH5) and their progressive restriction are also involved in specifying the retinal ganglion cell, the founding neural cell type in the mammalian retina. Thus, identifying factors that are involved in regulating the expression of Atonal during development are important to fully understand how retinal neurogenesis is accomplished. We have performed a chemical mutagenesis screen for autosomal dominant enhancers of a loss-of-function atonal eye phenotype. We report here the identification of five genes required for proper Atonal expression, three of which are novel regulators of Atonal expression in the Drosophila retina. We characterize the role of the daughterless, kismet, and roughened eye genes on atonal transcriptional regulation in the developing retina and show that each gene regulates atonal transcription differently within the context of retinal development. Our results provide additional insights into the regulation of Atonal expression in the developing Drosophila retina. PMID:18832354

  15. Early Adolescent Ego Development.

    Science.gov (United States)

    James, Michael A.

    1980-01-01

    Presented are the theoretical characteristics of social identity in early adolescence (ages 10 to 15). It is suggested that no longer is identity thought to begin with adolescence, but may have its beginnings in the preteen years. The article draws heavily on Eriksonian concepts. (Editor/KC)

  16. Expression and function of the empty spiracles gene in olfactory sense organ development of Drosophila melanogaster.

    Science.gov (United States)

    Sen, Sonia; Hartmann, Beate; Reichert, Heinrich; Rodrigues, Veronica

    2010-11-01

    In Drosophila, the cephalic gap gene empty spiracles plays key roles in embryonic patterning of the peripheral and central nervous system. During postembryonic development, it is involved in the development of central olfactory circuitry in the antennal lobe of the adult. However, its possible role in the postembryonic development of peripheral olfactory sense organs has not been investigated. Here, we show that empty spiracles acts in a subset of precursors that generate the olfactory sense organs of the adult antenna. All empty spiracles-expressing precursor cells co-express the proneural gene amos and the early patterning gene lozenge. Moreover, the expression of empty spiracles in these precursor cells is dependent on both amos and lozenge. Functional analysis reveals two distinct roles of empty spiracles in the development of olfactory sense organs. Genetic interaction studies in a lozenge-sensitized background uncover a requirement of empty spiracles in the formation of trichoid and basiconic olfactory sensilla. MARCM-based clonal mutant analysis reveals an additional role during axonal targeting of olfactory sensory neurons to glomeruli within the antennal lobe. Our findings on empty spiracles action in olfactory sense organ development complement previous studies that demonstrate its requirement in olfactory interneurons and, taken together with studies on the murine homologs of empty spiracles, suggest that conserved molecular genetic programs might be responsible for the formation of both peripheral and central olfactory circuitry in insects and mammals.

  17. Gene Expression Associated with Early and Late Chronotypes in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Mirko ePegoraro

    2015-05-01

    Full Text Available The circadian clock provides the temporal framework for rhythmic behavioural and metabolic functions. In the modern era of industrialization, work and social pressures, the clock function is often jeopardized, resulting in adverse and chronic effects on health. Understanding circadian clock function, particularly individual variation in diurnal phase preference (chronotype, and the molecular mechanisms underlying such chronotypes may lead to interventions that could abrogate clock dysfunction and improve human (and animal health and welfare. Our preliminary studies suggested that fruitflies, like humans, can be classified as early rising ‘larks’ or late rising ‘owls’, providing a convenient model system for these types of studies. We have identified strains of flies showing increased preference for morning emergence (Early or E from the pupal case, or more pronounced preference for evening emergence (Late or L. We have sampled pupae the day before eclosion (4th day after pupariation at 4 h intervals in the E and L strains, and examined differences in gene expression by RNAseq. We have identified differentially expressed transcripts between the E and L strains which provide candidate genes for studies of Drosophila chronotypes and their human orthologues.

  18. Dynamics of nuclear matrix proteome during embryonic development in Drosophila melanogaster

    Indian Academy of Sciences (India)

    Parul Varma; Rakesh K Mishra

    2011-08-01

    Embryonic development is a complex and dynamic process that involves spatiotemporal expression of genes in a highly coordinated manner. Multiple levels of nuclear architecture maintain the fidelity of gene expression programme. One of the components of nuclear architecture, which is believed to play an important role in regulation of gene expression, is the nuclear matrix (NuMat). Many studies over the past few years have tried to analyse the components of this non-chromatin scaffolding of the nucleus and have provided evidences of its structural and functional complexity. However, the relationship of NuMat with the process of embryonic development still remains poorly understood. Here, we report a comparative analysis of the NuMat proteomes of early and late stage Drosophila melanogaster embryos and show that 65% of the NuMat proteome is dynamic during development. Our study establishes links between the dynamics of nuclear architecture and embryonic development and provides tools to further understand the process such as cellular differentiation in the context of higher-order nuclear organization.

  19. Temporal patterns of broad isoform expression during the development of neuronal lineages in Drosophila

    Directory of Open Access Journals (Sweden)

    Williams Darren W

    2009-11-01

    Full Text Available Abstract Background During the development of the central nervous system (CNS of Drosophila, neuronal stem cells, the neuroblasts (NBs, first generate a set of highly diverse neurons, the primary neurons that mature to control larval behavior, and then more homogeneous sets of neurons that show delayed maturation and are primarily used in the adult. These latter, 'secondary' neurons show a complex pattern of expression of broad, which encodes a transcription factor usually associated with metamorphosis, where it acts as a key regulator in the transitions from larva and pupa. Results The Broad-Z3 (Br-Z3 isoform appears transiently in most central neurons during embryogenesis, but persists in a subset of these cells through most of larval growth. Some of the latter are embryonic-born secondary neurons, whose development is arrested until the start of metamorphosis. However, the vast bulk of the secondary neurons are generated during larval growth and bromodeoxyuridine incorporation shows that they begin expressing Br-Z3 about 7 hours after their birth, approximately the time that they have finished outgrowth to their initial targets. By the start of metamorphosis, the oldest secondary neurons have turned off Br-Z3 expression, while the remainder, with the exception of the very youngest, maintain Br-Z3 while they are interacting with potential partners in preparation for neurite elaboration. That Br-Z3 may be involved in early sprouting is suggested by ectopically expressing this isoform in remodeling primary neurons, which do not normally express Br-Z3. These cells now sprout into ectopic locations. The expression of Br-Z3 is transient and seen in all interneurons, but two other isoforms, Br-Z4 and Br-Z1, show a more selective expression. Analysis of MARCM clones shows that the Br-Z4 isoform is expressed by neurons in virtually all lineages, but only in those cells born during a window during the transition from the second to the third larval

  20. Drosophila genomes and the development of affordable molecular markers for species genotyping.

    Science.gov (United States)

    Minuk, Leigh; Civetta, Alberto

    2011-04-01

    The recent completion of genome sequencing of 12 species of Drosophila has provided a powerful resource for hypothesis testing, as well as the development of technical tools. Here we take advantage of genome sequence data from two closely related species of Drosophila, Drosophila simulans and Drosophila sechellia, to quickly identify candidate molecular markers for genotyping based on expected insertion or deletion (indel) differences between species. Out of 64 candidate molecular markers selected along the second and third chromosome of Drosophila, 51 molecular markers were validated using PCR and gel electrophoresis. We found that the 20% error rate was due to sequencing errors in the genome data, although we cannot rule out possible indel polymorphisms. The approach has the advantage of being affordable and quick, as it only requires the use of bioinformatics tools for predictions and a PCR and agarose gel based assay for validation. Moreover, the approach could be easily extended to a wide variety of taxa with the only limitation being the availability of complete or partial genome sequence data.

  1. Depleting Gene Activities in Early Drosophila Embryos with the “Maternal-Gal4–shRNA” System

    Science.gov (United States)

    Staller, Max V.; Yan, Dong; Randklev, Sakara; Bragdon, Meghan D.; Wunderlich, Zeba B.; Tao, Rong; Perkins, Lizabeth A.; DePace, Angela H.; Perrimon, Norbert

    2013-01-01

    In a developing Drosophila melanogaster embryo, mRNAs have a maternal origin, a zygotic origin, or both. During the maternal–zygotic transition, maternal products are degraded and gene expression comes under the control of the zygotic genome. To interrogate the function of mRNAs that are both maternally and zygotically expressed, it is common to examine the embryonic phenotypes derived from female germline mosaics. Recently, the development of RNAi vectors based on short hairpin RNAs (shRNAs) effective during oogenesis has provided an alternative to producing germline clones. Here, we evaluate the efficacies of: (1) maternally loaded shRNAs to knockdown zygotic transcripts and (2) maternally loaded Gal4 protein to drive zygotic shRNA expression. We show that, while Gal4-driven shRNAs in the female germline very effectively generate phenotypes for genes expressed maternally, maternally loaded shRNAs are not very effective at generating phenotypes for early zygotic genes. However, maternally loaded Gal4 protein is very efficient at generating phenotypes for zygotic genes expressed during mid-embryogenesis. We apply this powerful and simple method to unravel the embryonic functions of a number of pleiotropic genes. PMID:23105012

  2. Depleting gene activities in early Drosophila embryos with the "maternal-Gal4-shRNA" system.

    Science.gov (United States)

    Staller, Max V; Yan, Dong; Randklev, Sakara; Bragdon, Meghan D; Wunderlich, Zeba B; Tao, Rong; Perkins, Lizabeth A; Depace, Angela H; Perrimon, Norbert

    2013-01-01

    In a developing Drosophila melanogaster embryo, mRNAs have a maternal origin, a zygotic origin, or both. During the maternal-zygotic transition, maternal products are degraded and gene expression comes under the control of the zygotic genome. To interrogate the function of mRNAs that are both maternally and zygotically expressed, it is common to examine the embryonic phenotypes derived from female germline mosaics. Recently, the development of RNAi vectors based on short hairpin RNAs (shRNAs) effective during oogenesis has provided an alternative to producing germline clones. Here, we evaluate the efficacies of: (1) maternally loaded shRNAs to knockdown zygotic transcripts and (2) maternally loaded Gal4 protein to drive zygotic shRNA expression. We show that, while Gal4-driven shRNAs in the female germline very effectively generate phenotypes for genes expressed maternally, maternally loaded shRNAs are not very effective at generating phenotypes for early zygotic genes. However, maternally loaded Gal4 protein is very efficient at generating phenotypes for zygotic genes expressed during mid-embryogenesis. We apply this powerful and simple method to unravel the embryonic functions of a number of pleiotropic genes.

  3. Development of diet-induced insulin resistance in adult Drosophila melanogaster.

    Science.gov (United States)

    Morris, Siti Nur Sarah; Coogan, Claire; Chamseddin, Khalil; Fernandez-Kim, Sun Ok; Kolli, Santharam; Keller, Jeffrey N; Bauer, Johannes H

    2012-08-01

    The fruit fly Drosophila melanogaster is increasingly utilized as an alternative to costly rodent models to study human diseases. Fly models exist for a wide variety of human conditions, such as Alzheimer's and Parkinson's Disease, or cardiac function. Advantages of the fly system are its rapid generation time and its low cost. However, the greatest strength of the fly system are the powerful genetic tools that allow for rapid dissection of molecular disease mechanisms. Here, we describe the diet-dependent development of metabolic phenotypes in adult fruit flies. Depending on the specific type of nutrient, as well as its relative quantity in the diet, flies show weight gain and changes in the levels of storage macromolecules. Furthermore, the activity of insulin-signaling in the major metabolic organ of the fly, the fat body, decreases upon overfeeding. This decrease in insulin-signaling activity in overfed flies is moreover observed when flies are challenged with an acute food stimulus, suggesting that overfeeding leads to insulin resistance. Similar changes were observed in aging flies, with the development of the insulin resistance-like phenotype beginning at early middle ages. Taken together, these data demonstrate that imbalanced diet disrupts metabolic homeostasis in adult D. melanogaster and promotes insulin-resistant phenotypes. Therefore, the fly system may be a useful alternative tool in the investigation of molecular mechanisms of insulin resistance and the development of pharmacologic treatment options.

  4. A Model of the Spatio-temporal Dynamics of Drosophila Eye Disc Development

    Science.gov (United States)

    Fried, Patrick; Sánchez-Aragón, Máximo; Lehtinen, Birgitta; Casares, Fernando; Iber, Dagmar

    2016-01-01

    Patterning and growth are linked during early development and have to be tightly controlled to result in a functional tissue or organ. During the development of the Drosophila eye, this linkage is particularly clear: the growth of the eye primordium mainly results from proliferating cells ahead of the morphogenetic furrow (MF), a moving signaling wave that sweeps across the tissue from the posterior to the anterior side, that induces proliferating cells anterior to it to differentiate and become cell cycle quiescent in its wake. Therefore, final eye disc size depends on the proliferation rate of undifferentiated cells and on the speed with which the MF sweeps across the eye disc. We developed a spatio-temporal model of the growing eye disc based on the regulatory interactions controlled by the signals Decapentaplegic (Dpp), Hedgehog (Hh) and the transcription factor Homothorax (Hth) and explored how the signaling patterns affect the movement of the MF and impact on eye disc growth. We used published and new quantitative data to parameterize the model. In particular, two crucial parameter values, the degradation rate of Hth and the diffusion coefficient of Hh, were measured. The model is able to reproduce the linear movement of the MF and the termination of growth of the primordium. We further show that the model can explain several mutant phenotypes, but fails to reproduce the previously observed scaling of the Dpp gradient in the anterior compartment. PMID:27626238

  5. Oral magnetite nanoparticles disturb the development of Drosophila melanogaster from oogenesis to adult emergence.

    Science.gov (United States)

    Chen, Hanqing; Wang, Bing; Feng, Weiyue; Du, Wei; Ouyang, Hong; Chai, Zhifang; Bi, Xiaolin

    2015-05-01

    The potential impacts of nanomaterials (NMs) on fetal development have attracted great concerns because of the increased potential exposure to NMs during pregnancy. Drosophila melanogaster oogenesis and developmental transitions may provide an attractive system to study the biological and environmental effects of NMs on the embryonic development. In this study, the effects of three types of magnetite (Fe3O4) nanoparticles (MNPs): UN-MNPs (pristine), CA-MNPs (citric acid modified) and APTS-MNPs (3-aminopropyltriethoxylsilane coated) on the development of Drosophila at 300 and 600 μg/g dosage were studied. The uptake of MNPs by female and male flies caused obvious reduction in the female fecundity, and the developmental delay at the egg-pupae and pupae-adult transitions, especially in those treated by the positive APTS-MNPs. Further investigation demonstrates that the parental uptake of MNPs disturbs the oogenesis period, induces ovarian defect, reduces the length of eggs, decreases the number of nurse cells and delays egg chamber development, which may contribute to the decrease of fecundity of female Drosophila and the development delay of their offspring. Using the synchrotron radiation-based micro-X-ray fluorescence (SR-μXRF), the dyshomeostasis of trace elements such as Fe, Ca and Cu along the anterior-posterior axis of the fertilized eggs was found, which may be an important reason for the development delay of Drosophila.

  6. Drosophila melanogaster as a model system for assessing development under conditions of microgravity

    Science.gov (United States)

    Abbott, M. K.; Hilgenfeld, R. B.; Denell, R. E.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    More is known about the regulation of early developmental events in Drosophila than any other animal. In addition, its size and short life cycle make it a facile experimental system. Since developmental perturbations have been demonstrated when both oogenesis and embryogenesis occur in the space environment, there is a strong rationale for using this organism for the elucidation of specific gravity-sensitive developmental events.

  7. Digital three-dimensional models of Drosophila development.

    Science.gov (United States)

    Pereanu, Wayne; Hartenstein, Volker

    2004-08-01

    Digital models of organs, cells and subcellular structures have become important tools in biological and medical research. Reaching far beyond their traditional widespread use as didactic tools, computer-generated models serve as electronic atlases to identify specific elements in complex patterns, and as analytical tools that reveal relationships between such pattern elements that would remain obscure in two-dimensional sections. Digital models also offer the unique opportunity to store and display gene-expression patterns, and pilot studies have been made in several genetic model organisms, including mouse, Drosophila and Caenorhabditis elegans, to construct digital graphic databases intended as repositories for gene-expression data.

  8. Embryonic expression of Drosophila IMP in the developing CNS and PNS

    DEFF Research Database (Denmark)

    Adolph, Sidsel Kramshøj; Delotto, Robert; Nielsen, Finn Cilius;

    2008-01-01

    Drosophila IMP (dIMP) is related to the vertebrate RNA-binding proteins IMP1-3, ZBP1, Vg1RBP and CRD-BP, which are involved in RNA regulatory processes such as translational repression, localization and stabilization. The proteins are expressed in many fetal tissues, including the developing nerv...

  9. Comparative gene expression analysis of Dtg, a novel target gene of Dpp signaling pathway in the early Drosophila melanogaster embryo.

    Science.gov (United States)

    Hodar, Christian; Zuñiga, Alejandro; Pulgar, Rodrigo; Travisany, Dante; Chacon, Carlos; Pino, Michael; Maass, Alejandro; Cambiazo, Verónica

    2014-02-10

    In the early Drosophila melanogaster embryo, Dpp, a secreted molecule that belongs to the TGF-β superfamily of growth factors, activates a set of downstream genes to subdivide the dorsal region into amnioserosa and dorsal epidermis. Here, we examined the expression pattern and transcriptional regulation of Dtg, a new target gene of Dpp signaling pathway that is required for proper amnioserosa differentiation. We showed that the expression of Dtg was controlled by Dpp and characterized a 524-bp enhancer that mediated expression in the dorsal midline, as well as, in the differentiated amnioserosa in transgenic reporter embryos. This enhancer contained a highly conserved region of 48-bp in which bioinformatic predictions and in vitro assays identified three Mad binding motifs. Mutational analysis revealed that these three motifs were necessary for proper expression of a reporter gene in transgenic embryos, suggesting that short and highly conserved genomic sequences may be indicative of functional regulatory regions in D. melanogaster genes. Dtg orthologs were not detected in basal lineages of Dipterans, which unlike D. melanogaster develop two extra-embryonic membranes, amnion and serosa, nevertheless Dtg orthologs were identified in the transcriptome of Musca domestica, in which dorsal ectoderm patterning leads to the formation of a single extra-embryonic membrane. These results suggest that Dtg was recruited as a new component of the network that controls dorsal ectoderm patterning in the lineage leading to higher Cyclorrhaphan flies, such as D. melanogaster and M. domestica. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. The presence of nuclear cactus in the early Drosophila embryo may extend the dynamic range of the dorsal gradient.

    Directory of Open Access Journals (Sweden)

    Michael D O'Connell

    2015-04-01

    Full Text Available In a developing embryo, the spatial distribution of a signaling molecule, or a morphogen gradient, has been hypothesized to carry positional information to pattern tissues. Recent measurements of morphogen distribution have allowed us to subject this hypothesis to rigorous physical testing. In the early Drosophila embryo, measurements of the morphogen Dorsal, which is a transcription factor responsible for initiating the earliest zygotic patterns along the dorsal-ventral axis, have revealed a gradient that is too narrow to pattern the entire axis. In this study, we use a mathematical model of Dorsal dynamics, fit to experimental data, to determine the ability of the Dorsal gradient to regulate gene expression across the entire dorsal-ventral axis. We found that two assumptions are required for the model to match experimental data in both Dorsal distribution and gene expression patterns. First, we assume that Cactus, an inhibitor that binds to Dorsal and prevents it from entering the nuclei, must itself be present in the nuclei. And second, we assume that fluorescence measurements of Dorsal reflect both free Dorsal and Cactus-bound Dorsal. Our model explains the dynamic behavior of the Dorsal gradient at lateral and dorsal positions of the embryo, the ability of Dorsal to regulate gene expression across the entire dorsal-ventral axis, and the robustness of gene expression to stochastic effects. Our results have a general implication for interpreting fluorescence-based measurements of signaling molecules.

  11. The Presence of Nuclear Cactus in the Early Drosophila Embryo May Extend the Dynamic Range of the Dorsal Gradient

    Science.gov (United States)

    O’Connell, Michael D.; Reeves, Gregory T.

    2015-01-01

    In a developing embryo, the spatial distribution of a signaling molecule, or a morphogen gradient, has been hypothesized to carry positional information to pattern tissues. Recent measurements of morphogen distribution have allowed us to subject this hypothesis to rigorous physical testing. In the early Drosophila embryo, measurements of the morphogen Dorsal, which is a transcription factor responsible for initiating the earliest zygotic patterns along the dorsal-ventral axis, have revealed a gradient that is too narrow to pattern the entire axis. In this study, we use a mathematical model of Dorsal dynamics, fit to experimental data, to determine the ability of the Dorsal gradient to regulate gene expression across the entire dorsal-ventral axis. We found that two assumptions are required for the model to match experimental data in both Dorsal distribution and gene expression patterns. First, we assume that Cactus, an inhibitor that binds to Dorsal and prevents it from entering the nuclei, must itself be present in the nuclei. And second, we assume that fluorescence measurements of Dorsal reflect both free Dorsal and Cactus-bound Dorsal. Our model explains the dynamic behavior of the Dorsal gradient at lateral and dorsal positions of the embryo, the ability of Dorsal to regulate gene expression across the entire dorsal-ventral axis, and the robustness of gene expression to stochastic effects. Our results have a general implication for interpreting fluorescence-based measurements of signaling molecules. PMID:25879657

  12. Lack of miRNA misregulation at early pathological stages in Drosophila neurodegenerative disease models

    Directory of Open Access Journals (Sweden)

    Anita eReinhardt

    2012-10-01

    Full Text Available Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80-84 year old Europeans or Parkinson disease (PD, 1.4% prevalence for > 55 years old share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence and frontotemporal lobar degeneration (FTLD, 0.02% prevalence, a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs, a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for 7 diseases (PD, 3 FTLD, 3 dominant ataxias that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non coding CAG repeat RNAs (sCAG in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

  13. DTL, the Drosophila homolog of PIMT/Tgs1 nuclear receptor coactivator-interacting protein/RNA methyltransferase, has an essential role in development.

    Science.gov (United States)

    Komonyi, Orbán; Pápai, Gábor; Enunlu, Izzet; Muratoglu, Selen; Pankotai, Tibor; Kopitova, Darija; Maróy, Péter; Udvardy, Andor; Boros, Imre

    2005-04-01

    We describe a novel Drosophila gene, dtl (Drosophila Tat-like), which encodes a 60-kDa protein with RNA binding activity and a methyltransferase (MTase) domain. Dtl has an essential role in Drosophila development. The homologs of DTL recently described include PIMT (peroxisome proliferator-activated receptor-interacting protein with a methyltransferase domain), an RNA-binding protein that interacts with and enhances the nuclear receptor coactivator function, and TGS1, the methyltransferase involved in the formation of the 2,2,7-trimethylguanosine (m3G) cap of non-coding small RNAs. DTL is expressed throughout all of the developmental stages of Drosophila. The dtl mRNA has two ORFs (uORF and dORF). The product of dORF is the 60-kDa PIMT/TGS1 homolog protein that is translated from an internal AUG located 538 bp downstream from the 5' end of the message. This product of dtl is responsible for the formation of the m3G cap of small RNAs of Drosophila. Trimethylguanosine synthase activity is essential in Drosophila. The deletion in the dORF or point mutation in the putative MTase active site results in a reduced pool of m3G cap-containing RNAs and lethality in the early pupa stage. The 5' region of the dtl message also has the coding capacity (uORF) for a 178 amino acid protein. For complete rescue of the lethal phenotype of dtl mutants, the presence of the entire dtl transcription unit is required. Transgenes that carry mutations within the uORF restore the MTase activity but result in only partial rescue of the lethal phenotype. Interestingly, two transgenes bearing a mutation in uORF or dORF in trans can result in complete rescue.

  14. The gene transformer-2 of Sciara (Diptera, Nematocera and its effect on Drosophila sexual development

    Directory of Open Access Journals (Sweden)

    Ruiz María F

    2011-03-01

    Full Text Available Abstract Background The gene transformer-2, which is involved in sex determination, has been studied in Drosophila, Musca, Ceratitis, Anastrepha and Lucilia. All these members of Diptera belong to the suborder Brachycera. In this work, it is reported the isolation and characterisation of genes transformer-2 of the dipterans Sciara ocellaris and Bradysia coprophila (formerly Sciara coprophila, which belong to the much less extensively analysed Sciaridae Family of the Suborder Nematocera, which is paraphyletic with respect to Suborder Brachycera. Results The transformer-2 genes of the studied Sciara species were found to be transcribed in both sexes during development and adult life, in both the soma and germ lines. They produced a single primary transcript, which follows the same alternative splicing in both sexes, giving rise to different mRNAs isoforms. In S. ocellaris the most abundant mRNA isoform encoded a full-length protein of 251 amino acids, while that of B. coprophila encoded a protein of 246 amino acids. Both showed the features of the SR protein family. The less significant mRNA isoforms of both species encoded truncated, presumably non-functional Transformer-2 proteins. The comparison of the functional Sciara Transformer-2 proteins among themselves and those of other insects revealed the greatest degree of conservation in the RRM domain and linker region. In contrast, the RS1 and RS2 domains showed extensive variation with respect to their number of amino acids and their arginine-serine (RS dipeptide content. The expression of S. ocellaris Transformer-2 protein in Drosophila XX pseudomales lacking the endogenous transformer-2 function caused their partial feminisation. Conclusions The transformer-2 genes of both Sciaridae species encode a single protein in both sexes that shares the characteristics of the Transformer-2 proteins of other insects. These proteins showed conserved sex-determination function in Drosophila; i.e., they were

  15. The gene transformer-2 of Sciara (Diptera, Nematocera) and its effect on Drosophila sexual development.

    Science.gov (United States)

    Martín, Iker; Ruiz, María F; Sánchez, Lucas

    2011-03-15

    The gene transformer-2, which is involved in sex determination, has been studied in Drosophila, Musca, Ceratitis, Anastrepha and Lucilia. All these members of Diptera belong to the suborder Brachycera. In this work, it is reported the isolation and characterisation of genes transformer-2 of the dipterans Sciara ocellaris and Bradysia coprophila (formerly Sciara coprophila), which belong to the much less extensively analysed Sciaridae Family of the Suborder Nematocera, which is paraphyletic with respect to Suborder Brachycera. The transformer-2 genes of the studied Sciara species were found to be transcribed in both sexes during development and adult life, in both the soma and germ lines. They produced a single primary transcript, which follows the same alternative splicing in both sexes, giving rise to different mRNAs isoforms. In S. ocellaris the most abundant mRNA isoform encoded a full-length protein of 251 amino acids, while that of B. coprophila encoded a protein of 246 amino acids. Both showed the features of the SR protein family. The less significant mRNA isoforms of both species encoded truncated, presumably non-functional Transformer-2 proteins. The comparison of the functional Sciara Transformer-2 proteins among themselves and those of other insects revealed the greatest degree of conservation in the RRM domain and linker region. In contrast, the RS1 and RS2 domains showed extensive variation with respect to their number of amino acids and their arginine-serine (RS) dipeptide content. The expression of S. ocellaris Transformer-2 protein in Drosophila XX pseudomales lacking the endogenous transformer-2 function caused their partial feminisation. The transformer-2 genes of both Sciaridae species encode a single protein in both sexes that shares the characteristics of the Transformer-2 proteins of other insects. These proteins showed conserved sex-determination function in Drosophila; i.e., they were able to form a complex with the endogenous Drosophila

  16. A transcriptional network controlling glial development in the Drosophila visual system.

    Science.gov (United States)

    Bauke, Ann-Christin; Sasse, Sofia; Matzat, Till; Klämbt, Christian

    2015-06-15

    In the nervous system, glial cells need to be specified from a set of progenitor cells. In the developing Drosophila eye, perineurial glia proliferate and differentiate as wrapping glia in response to a neuronal signal conveyed by the FGF receptor pathway. To unravel the underlying transcriptional network we silenced all genes encoding predicted DNA-binding proteins in glial cells using RNAi. Dref and other factors of the TATA box-binding protein-related factor 2 (TRF2) complex were previously predicted to be involved in cellular metabolism and cell growth. Silencing of these genes impaired early glia proliferation and subsequent differentiation. Dref controls proliferation via activation of the Pdm3 transcription factor, whereas glial differentiation is regulated via Dref and the homeodomain protein Cut. Cut expression is controlled independently of Dref by FGF receptor activity. Loss- and gain-of-function studies show that Cut is required for glial differentiation and is sufficient to instruct the formation of membrane protrusions, a hallmark of wrapping glial morphology. Our work discloses a network of transcriptional regulators controlling the progression of a naïve perineurial glia towards the fully differentiated wrapping glia.

  17. Spire, an actin nucleation factor, regulates cell division during Drosophila heart development.

    Directory of Open Access Journals (Sweden)

    Peng Xu

    Full Text Available The Drosophila dorsal vessel is a beneficial model system for studying the regulation of early heart development. Spire (Spir, an actin-nucleation factor, regulates actin dynamics in many developmental processes, such as cell shape determination, intracellular transport, and locomotion. Through protein expression pattern analysis, we demonstrate that the absence of spir function affects cell division in Myocyte enhancer factor 2-, Tinman (Tin-, Even-skipped- and Seven up (Svp-positive heart cells. In addition, genetic interaction analysis shows that spir functionally interacts with Dorsocross, tin, and pannier to properly specify the cardiac fate. Furthermore, through visualization of double heterozygous embryos, we determines that spir cooperates with CycA for heart cell specification and division. Finally, when comparing the spir mutant phenotype with that of a CycA mutant, the results suggest that most Svp-positive progenitors in spir mutant embryos cannot undergo full cell division at cell cycle 15, and that Tin-positive progenitors are arrested at cell cycle 16 as double-nucleated cells. We conclude that Spir plays a crucial role in controlling dorsal vessel formation and has a function in cell division during heart tube morphogenesis.

  18. The mechanism of pattern formation in the developing drosophila retina

    Institute of Scientific and Technical Information of China (English)

    SUN QiCheng

    2007-01-01

    The biological patterning of the drosophila retina in vivo has striking resemblance to liquid bubbles, in which the surface mechanics due to N-cadherin within a sub-group of retina cells can be mimicked by surface tension. In this work, the aggregating patterns were reasonably simplified into 2D clusters consisting of 2-6 identical bubbles confined within a shrinking boundary. By using a hybrid fluid dynamics model proposed for liquid foams, the aggregating process of 2-6 retina cells was studied. Assuming the minimal perimeter for patterning cells to be the condition of stability patterns, the stable converged patterns we simulated in this work are the same as the experimental observations. More importantly, a new pattern of 6 cells was obtained which was found physically more stable than the other two reported by Hayashi and Carthew[1]. Aggregating perimeters of cells, i.e. the surface energy, showed a good linear fit with the cell numbers.

  19. The mechanism of pattern formation in the developing drosophila retina

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The biological patterning of the drosophila retina in vivo has striking resemblance to liquid bubbles, in which the surface mechanics due to N-cadherin within a sub-group of retina cells can be mimicked by surface tension. In this work, the aggregating patterns were reasonably simplified into 2D clusters consisting of 2—6 identical bubbles confined within a shrinking boundary. By using a hybrid fluid dy-namics model proposed for liquid foams, the aggregating process of 2―6 retina cells was studied. Assuming the minimal perimeter for patterning cells to be the condition of stability patterns, the stable converged patterns we simulated in this work are the same as the experimental observations. More importantly, a new pattern of 6 cells was obtained which was found physically more stable than the other two reported by Hayashi and Carthew[1]. Aggregating perimeters of cells, i.e. the surface energy, showed a good linear fit with the cell numbers.

  20. Modeling congenital disease and inborn errors of development in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Matthew J. Moulton

    2016-03-01

    Full Text Available Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence, include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes.

  1. Modeling congenital disease and inborn errors of development in Drosophila melanogaster.

    Science.gov (United States)

    Moulton, Matthew J; Letsou, Anthea

    2016-03-01

    Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes.

  2. Drosophila Kismet regulates histone H3 lysine 27 methylation and early elongation by RNA polymerase II.

    Directory of Open Access Journals (Sweden)

    Shrividhya Srinivasan

    2008-10-01

    Full Text Available Polycomb and trithorax group proteins regulate cellular pluripotency and differentiation by maintaining hereditable states of transcription. Many Polycomb and trithorax group proteins have been implicated in the covalent modification or remodeling of chromatin, but how they interact with each other and the general transcription machinery to regulate transcription is not well understood. The trithorax group protein Kismet-L (KIS-L is a member of the CHD subfamily of chromatin-remodeling factors that plays a global role in transcription by RNA polymerase II (Pol II. Mutations in CHD7, the human counterpart of kis, are associated with CHARGE syndrome, a developmental disorder affecting multiple tissues and organs. To clarify how KIS-L activates gene expression and counteracts Polycomb group silencing, we characterized defects resulting from the loss of KIS-L function in Drosophila. These studies revealed that KIS-L acts downstream of P-TEFb recruitment to stimulate elongation by Pol II. The presence of two chromodomains in KIS-L suggested that its recruitment or function might be regulated by the methylation of histone H3 lysine 4 by the trithorax group proteins ASH1 and TRX. Although we observed significant overlap between the distributions of KIS-L, ASH1, and TRX on polytene chromosomes, KIS-L did not bind methylated histone tails in vitro, and loss of TRX or ASH1 function did not alter the association of KIS-L with chromatin. By contrast, loss of kis function led to a dramatic reduction in the levels of TRX and ASH1 associated with chromatin and was accompanied by increased histone H3 lysine 27 methylation-a modification required for Polycomb group repression. A similar increase in H3 lysine 27 methylation was observed in ash1 and trx mutant larvae. Our findings suggest that KIS-L promotes early elongation and counteracts Polycomb group repression by recruiting the ASH1 and TRX histone methyltransferases to chromatin.

  3. CELLULAR LOCALIZATION AND EXPRESSION OF pygo DURING DROSOPHILA DEVELOPMENT

    Institute of Scientific and Technical Information of China (English)

    LINXin-da; LINXin-hua; CHENGJia-an

    2003-01-01

    Wg/Wnt signaling is a key signaling pathway in Drosophila. Many genes involved in Wingless(wg) signal transduction pathway downstream of Wg, or it'' s vertebrate Wg homologue Wnt, have been identified.Transduction of the Wg signal downstream of Wg is mediated by nuclear TCF/LEF-1, through association with Ar-madillo (Arm)/β-catenin. Pygopus (pygo) is a new identified component in this pathway . Cellular localization experiment showed that pygo was expressed specifically in the nucleus. The expression profile of pygo in embryos was examined using in situ hybridization. Although pygo expressed ubiquitously in the embryos, it expressed at relatively high level in pre-blastoderm embryos which indicate a high degree of maternally provided message, fol-lowed by a low level of ubiquitous zygotic expression. This continues into larval tissues (including wing disc, eye disc and leg disc), where pygo appears to be expressed at low level. Comparison of pygo expression levels, in the wing disc, eye disc and leg disc, showed pygo expression level in the wing disc pouch and leg disc were rela-tive higher.

  4. [From random mutagenesis to precise genome editing: the development and evolution of genome editing techniques in Drosophila].

    Science.gov (United States)

    Su, Fang; Huang, Zongliang; Guo, Yawen; Jiao, Renjie; Zi, Li; Chen, Jianming; Liu, Jiyong

    2016-01-01

    Drosophila melanogaster, an important model organism for studying life science, has contributed more to the research of genetics, developmental biology and biomedicine with the development of genome editing techniques. Drosophila genome-editing techniques have evolved from random mutagenesis to precise genome editing and from simple mutant construction to diverse genome editing methods since the 20th century. Chemical mutagenesis, using Ethyl methanesulfonate (EMS), is an important technique to study gene function in forward genetics, however, the precise knockout of Drosophila genes could not be achieved. The gene targeting technology, based on homologous recombination, has accomplished the precise editing of Drosophila genome for the first time, but with low efficiency. The CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein)-mediated precise genome editing is simple, fast and highly efficient compared with the gene targeting technology in Drosophila. In this review, we focus on Drosophila gene knockout, and summarize the evolution of genome editing techniques in Drosophila, emphasizing the development and applications of gene targeting, zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and CRISPR/Cas9 techniques.

  5. Depletion of ribosomal protein L8 impairs Drosophila development and is associated with apoptosis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Ribosomal protein L8 is a component of the 60S subunit of the ribosome and is involved in protein synthesis but its role in Drosophila development is not well understood.We depleted L8 through RNA interference (RNAi) to examine its effects on fly development both in vivo and in vitro.The results demonstrated that L8 RNAi caused embryonic or first-larval lethality,delay of larval development,defects in eye and wing morphology,and dramatically reduced the number of S2 cells.This indicated that L8 plays a crucial role in Drosophila development.Acridine orange staining of the wing discs showed that apoptosis occurred when L8 was depleted,indicating that depletion of L8 is tightly connected to apoptosis.RT-PCR analyses of the transcription level of genes that are known to be key factors in apoptosis (p53,hid,reaper,dark,Dcp-1) and cell cycle regulation (cdc45,MCM3,cyclin B,incenp) in L8-deficient S2 cells,were consistent with their role in apoptosis induction and cell cycle arrest.These results indicate that depletion of L8 strongly impairs Drosophila development,and that this depletion is associated with cell proliferation arrest and apoptosis,in which p53 may play a central role.

  6. Identification of retinal transformation hot spots in developing Drosophila epithelia.

    Directory of Open Access Journals (Sweden)

    Claire L Salzer

    Full Text Available BACKGROUND: The retinal determination (RD network is an evolutionarily conserved regulatory circuit that governs early events in the development of eyes throughout the animal kingdom. Ectopic expression of many members of this network leads to the transformation of non-retinal epithelia into eye tissue. An often-overlooked observation is that only particular cell-populations within a handful of tissues are capable of having their primary developmental instructions superseded and overruled. METHODOLOGY/PRELIMINARY FINDINGS: Here we confirm that indeed, only a discrete number of cell populations within the imaginal discs that give rise to the head, antenna, legs, wings and halteres have the cellular plasticity to have their developmental fates altered. In contrast to previous reports, we find that all transformable cell populations do not lie within the TGFbeta or Hedgehog signaling domains. Additionally neither signaling cascade alone is sufficient for non-retinal cell types to be converted into retinal tissue. The transformation "hot spots" that we have identified appear to coincide with several previously defined transdetermination "weak spots", suggesting that ectopic eye formation is less the result of one network overriding the orders of another, as previously thought, but rather is the physical manifestation of redirecting cell populations of enormous cellular plasticity. We also demonstrate that the initiation of eye formation in non-retinal tissues occurs asynchronously compared to that of the normal eye suggesting that retinal development is not under the control of a global developmental clock. CONCLUSIONS/SIGNIFICANCE: We conclude that the subregions of non-retinal tissues that are capable of supporting eye formation represent specialized cell-populations that have a different level of plasticity than other cells within these tissues and may be the founder cells of each tissue.

  7. The effect of space environment on the development and aging of Drosophila Melanogaster (7-IML-1)

    Science.gov (United States)

    Marco, Roberto

    1992-01-01

    This experiment involves the study of the development of eggs of the fly, Drosophila, exposed to microgravity. It is presumed that oogenesis, rather than further states of embryonic development, is sensitive to gravity. This hypothesis will be tested by collecting eggs layered at specific times inflight and postflight from flies exposed to 0 and 1 g. This portion of the experiment is a repetition of an earlier experiment flown in Biorack during the Spacelab D1 Mission. An added feature of the experiment for the First International Microgravity Laboratory (IML-1) Mission is to study the effect of microgravity on the life span of Drosophila male flies. Various aspects of the investigation are discussed.

  8. The deubiquitinating enzyme Usp5 regulates Notch and RTK signaling during Drosophila eye development.

    Science.gov (United States)

    Ling, Xuemei; Huang, Qinzhu; Xu, Yanqin; Jin, Yuxiao; Feng, Ying; Shi, Weijie; Ye, Xiaolei; Lin, Yi; Hou, Ling; Lin, Xinhua

    2017-03-01

    Usp5 belongs to the USP family of deubiquitinating enzymes (DUBs), which comprises the largest class of DUBs. We previously reported that loss of Usp5 impairs development of photoreceptors in Drosophila eyes, although the detailed mechanism remained unclear. In the present study, we demonstrate that Usp5 regulates both Notch and receptor tyrosine kinase (RTK) signaling. Loss of Usp5 results in upregulation of Notch signaling and downregulation of RTK signaling, leading to impaired photoreceptor development. Moreover, genetic rescue experiments with the DNA binding protein Suppressor of Hairless or Notch RNAi indicate that they mediate the regulation of RTK signaling by Usp5. The present study provides mechanistic insight into how Usp5 regulates photoreceptor differentiation by Notch and RTK signaling in the Drosophila eye. © 2017 Federation of European Biochemical Societies.

  9. Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development.

    Science.gov (United States)

    Halder, G; Callaerts, P; Flister, S; Walldorf, U; Kloter, U; Gehring, W J

    1998-06-01

    The Drosophila Pax-6 gene eyeless acts high up in the genetic hierarchy involved in compound eye development and can direct the formation of extra eyes in ectopic locations. Here we identify sine oculis and eyes absent as two mediators of the eye-inducing activity of eyeless. We show that eyeless induces and requires the expression of both genes independently during extra eye development. During normal eye development, eyeless is expressed earlier than and is required for the expression of sine oculis and eyes absent, but not vice versa. Based on the results presented here and those of others, we propose a model in which eyeless induces the initial expression of both sine oculis and eyes absent in the eye disc. sine oculis and eyes absent then appear to participate in a positive feedback loop that regulates the expression of all three genes. In contrast to the regulatory interactions that occur in the developing eye disc, we also show that in the embryonic head, sine oculis acts in parallel to eyeless and twin of eyeless, a second Pax-6 gene from Drosophila. Recent studies in vertebrate systems indicate that the epistatic relationships among the corresponding vertebrate homologs are very similar to those observed in Drosophila.

  10. Ectopic scute induces Drosophila ommatidia development without R8 founder photoreceptors

    OpenAIRE

    Sun, Yan; Jan, Lily Yeh; Jan, Yuh Nung

    2000-01-01

    During development of the Drosophila peripheral nervous system, different proneural genes encoding basic helix–loop–helix transcription factors are required for different sensory organs to form. atonal (ato) is the proneural gene required for chordotonal organs and R8 photoreceptors, whereas the achaete-scute complex contains proneural genes for external sensory organs such as the macrochaetae, large sensory bristles. Whereas ectopic ato expression induces chordotonal organ formation, ectopic...

  11. Modeling congenital disease and inborn errors of development in Drosophila melanogaster

    OpenAIRE

    2016-01-01

    Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze t...

  12. Modeling congenital disease and inborn errors of development in Drosophila melanogaster

    OpenAIRE

    2016-01-01

    ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to ...

  13. Use of Early Ripening Cultivars to Avoid Infestation and Mass Trapping to Manage Drosophila suzukii (Diptera: Drosophilidae) in Vaccinium corymbosum (Ericales: Ericaceae).

    Science.gov (United States)

    Hampton, Emily; Koski, Carissa; Barsoian, Olivia; Faubert, Heather; Cowles, Richard S; Alm, Steven R

    2014-10-01

    Use of early ripening highbush blueberry cultivars to avoid infestation and mass trapping were evaluated for managing spotted wing drosophila, Drosophila suzukii (Matsumura). Fourteen highbush blueberry cultivars were sampled for spotted wing drosophila infestation. Most 'Earliblue', 'Bluetta', and 'Collins' fruit were harvested before spotted wing drosophila oviposition commenced, and so escaped injury. Most fruit from 'Bluejay', 'Blueray', and 'Bluehaven' were also harvested before the first week of August, after which spotted wing drosophila activity led to high levels of blueberry infestation. In a separate experiment, damage to cultivars was related to the week in which fruit were harvested, with greater damage to fruit observed as the season progressed. Attractant traps placed within blueberry bushes increased nearby berry infestation by 5%, irrespective of cultivar and harvest date. The significant linear reduction in infestation with increasing distance from the attractant trap suggests that traps are influencing fly behavior to at least 5.5 m. Insecticides applied to the exterior of traps, compared with untreated traps, revealed that only 10-30% of flies visiting traps enter the traps and drown. Low trap efficiency may jeopardize surrounding fruits by increasing local spotted wing drosophila activity. To protect crops, traps for mass trapping should be placed in a perimeter outside fruit fields and insecticides need to be applied to the surface of traps or on nearby fruit to function as an attract-and-kill strategy. © 2014 Entomological Society of America.

  14. From the Eye to the Brain: Development of the Drosophila Visual System.

    Science.gov (United States)

    Nériec, Nathalie; Desplan, Claude

    2016-01-01

    How stem cells produce the huge diversity of neurons that form the visual system, and how these cells are assembled in neural circuits are a critical question in developmental neurobiology. Investigations in Drosophila have led to the discovery of several basic principles of neural patterning. In this chapter, we provide an overview of the field by describing the development of the Drosophila visual system, from the embryo to the adult and from the gross anatomy to the cellular level. We then explore the general molecular mechanisms identified that might apply to other neural structures in flies or in vertebrates. Finally, we discuss the major challenges that remain to be addressed in the field. © 2016 Elsevier Inc. All rights reserved.

  15. Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history.

    Science.gov (United States)

    Flatt, Thomas; Tu, Meng-Ping; Tatar, Marc

    2005-10-01

    Understanding how traits are integrated at the organismal level remains a fundamental problem at the interface of developmental and evolutionary biology. Hormones, regulatory signaling molecules that coordinate multiple developmental and physiological processes, are major determinants underlying phenotypic integration. The probably best example for this is the lipid-like juvenile hormone (JH) in insects. Here we review the manifold effects of JH, the most versatile animal hormone, with an emphasis on the fruit fly Drosophila melanogaster, an organism amenable to both genetics and endocrinology. JH affects a remarkable number of processes and traits in Drosophila development and life history, including metamorphosis, behavior, reproduction, diapause, stress resistance and aging. While many molecular details underlying JH signaling remain unknown, we argue that studying "hormonal pleiotropy" offers intriguing insights into phenotypic integration and the mechanisms underlying life history evolution. In particular, we illustrate the role of JH as a key mediator of life history trade-offs.

  16. Choreography of early thalamocortical development.

    Science.gov (United States)

    Molnár, Zoltán; Higashi, Shuji; López-Bendito, Guillermina

    2003-06-01

    Thalamic axons, which carry most of the information from the sensory environment, are amongst the first projections to reach the cerebral cortex during embryonic development. It has been proposed that the scaffold of early generated cells in the ventral thalamus, internal capsule and preplate play a pivotal role in their deployment through sharp gene expression boundaries. These ideas were recently evaluated in various strains of mutant mice. In Tbr1, Gbx2, Pax6 KO both thalamic and corticofugal projections fail to traverse the striatocortical junction. In both Emx2 and Pax6 KO brains, the misrouted thalamic afferents are accompanied by displacements of the pioneering projections from the internal capsule. Regardless of their altered route, thalamic afferents in the reeler and L1 KO mice seem to be able to redistribute themselves on the cortical sheet and establish normal periphery-related representation in the somatosensory cortex. Early neural activity delivered through the thalamic projections is thought to be involved in the realignment process of thalamic axons at the time of their accumulation in the subplate layer. However, axonal growth and the early topographic arrangement of thalamocortical fiber pathways appear normal in the Snap25 KO, where action potential mediated synaptic vesicle release is disrupted. We therefore suggest that intercellular communication mediated by constitutive secretion of transmitters or growth factors might play a dominant role during early thalamocortical development.

  17. Oral intake of zirconia nanoparticle alters neuronal development and behaviour of Drosophila melanogaster

    Science.gov (United States)

    Mishra, Monalisa; Sabat, Debabrat; Ekka, Basanti; Sahu, Swetapadma; P, Unnikannan; Dash, Priyabrat

    2017-08-01

    Zirconia nanoparticles (ZrO2 NPs) have been extensively used in teeth and bone implants and thus get a chance to interact with the physiological system. The current study investigated the oral administration of various concentrations of ZrO2 NPs synthesized by the hydrothermal method (0.25 to 5.0 mg L-1) on Drosophila physiology and behaviour. The size of the currently studied nanoparticle varies from 10 to 12 nm. ZrO2 NPs accumulated within the gut in a concentration-dependent manner and generate reactive oxygen species (ROS) only at 2.5 and 5.0 mg L-1 concentrations. ROS was detected by nitroblue tetrazolium (NBT) assay and 2',7'-dichlorofluorescein (http://www.ncbi.nlm.nih.gov/pubmed/20370560) (H2DCF) staining. The ROS toxicity alters the larval gut structure as revealed by DAPI staining. The NP stress of larvae affects the Drosophila development by distressing pupa count and varying the phenotypic changes in sensory organs (eye, thorax bristle, wings). Besides phenotypic changes, flawed climbing behaviour against gravity was seen in ZrO2 NP-treated flies. All together, for the first time, we have reported that a ROS-mediated ZrO2 NP toxicity alters neuronal development and functioning using Drosophila as a model organism. [Figure not available: see fulltext.

  18. Eyes absent tyrosine phosphatase activity is not required for Drosophila development or survival.

    Directory of Open Access Journals (Sweden)

    Meng Jin

    Full Text Available Eyes absent (Eya is an evolutionarily conserved transcriptional coactivator and protein phosphatase that regulates multiple developmental processes throughout the metazoans. Drosophila eya is necessary for survival as well as for the formation of the adult eye. Eya contains a tyrosine phosphatase domain, and mutations altering presumptive active-site residues lead to strongly reduced activities in ectopic eye induction, in vivo genetic rescue using the Gal4-UAS system, and in vitro phosphatase assays. However, these mutations have not been analyzed during normal development with the correct levels, timing, and patterns of endogenous eya expression. To investigate whether the tyrosine phosphatase activity of Eya plays a role in Drosophila survival or normal eye formation, we generated three eya genomic rescue (eyaGR constructs that alter key active-site residues and tested them in vivo. In striking contrast to previous studies, all eyaGR constructs fully restore eye formation as well as viability in an eya null mutant background. We conclude that the tyrosine phosphatase activity of Eya is not required for normal eye development or survival in Drosophila. Our study suggests the need for a re-evaluation of the mechanism of Eya action and underscores the importance of studying genes in their native context.

  19. Germline progenitors escape the widespread phenomenon of homolog pairing during Drosophila development.

    Directory of Open Access Journals (Sweden)

    Eric F Joyce

    Full Text Available Homolog pairing, which plays a critical role in meiosis, poses a potential risk if it occurs in inappropriate tissues or between nonallelic sites, as it can lead to changes in gene expression, chromosome entanglements, and loss-of-heterozygosity due to mitotic recombination. This is particularly true in Drosophila, which supports organismal-wide pairing throughout development. Discovered over a century ago, such extensive pairing has led to the perception that germline pairing in the adult gonad is an extension of the pairing established during embryogenesis and, therefore, differs from the mechanism utilized in most species to initiate pairing specifically in the germline. Here, we show that, contrary to long-standing assumptions, Drosophila meiotic pairing in the gonad is not an extension of pairing established during embryogenesis. Instead, we find that homologous chromosomes are unpaired in primordial germ cells from the moment the germline can be distinguished from the soma in the embryo and remain unpaired even in the germline stem cells of the adult gonad. We further establish that pairing originates immediately after the stem cell stage. This pairing occurs well before the initiation of meiosis and, strikingly, continues through the several mitotic divisions preceding meiosis. These discoveries indicate that the spatial organization of the Drosophila genome differs between the germline and the soma from the earliest moments of development and thus argue that homolog pairing in the germline is an active process as versus a passive continuation of pairing established during embryogenesis.

  20. Development of three Drosophila melanogaster strains with different sensitivity to volatile anesthetics

    Institute of Scientific and Technical Information of China (English)

    LIU Jin; HU Zhao-yang; YE Qi-quan; DAI Shuo-hua

    2009-01-01

    Background The mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.Methods Median effective doses (ED50) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6-10 were cultured for breeding sensitive offspring (S1). So did median ones of percentile 48-52 for breeding median offspring (M1), resistant ones of percentile 91-95 for breeding resistant offspring (R1). Process was repeated through 31 generations, in the 37th generation, S37,M37 and R37 were used to determine ED50 for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane,chloroform and trichloroethylene, then ED50 values were correlated with minimum alveolar concentration (MAC) values in human.Results From a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED50 values in three strains correlated directly with MAC values in human.Conclusions Three Drosophila me/anogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED50 are directly correlated with MAC in human for eight volatile anesthetics.

  1. Investigating the effects of nanoparticles on reproduction and development in Drosophila melanogaster and CD-1 mice

    Science.gov (United States)

    Philbrook, Nicola Anne

    Manufactured nanoparticles (NPs) are a class of small (≤ 100 nm) materials that are being used for a variety of purposes, including industrial lubricants, food additives, antibacterial agents, as well as delivery systems for drug and gene therapies. Their unique characteristics due to their small size as well as their parent materials allow them to be exploited in convenience applications; however, some of these properties also allow them to interact with and invade biological systems. Few studies have been performed to determine the potential harm that NPs can inflict on reproductive and developmental processes in organisms. In this study, Drosophila melanogaster and CD-1 mice were orally exposed to varying doses of titanium dioxide (TiO 2) NPs, silver (Ag) NPs, or hydroxyl-functionalized carbon nanotubes (fCNTs) and Drosophila were also exposed to microparticles (MPs) as a control for particle size. The subsequent effect of these materials on reproduction and development were evaluated. Strikingly, each type of NP studied negatively affected either reproduction or development in one or both of the two model systems. TiO2 NPs significantly negative effected both CD-1 mouse development (100 mg/kg or 1000 mg/kg) as well as Drosophila female fecundity (0.005%-0.5% w/v). Ag NPs significantly reduced mouse fetus viability after prenatal exposure to10 mg/kg. Ag NPs also significantly decreased the developmental success of Drosophila when they were directly exposed to these NPs (0.05% - 0.5% w/v) compared to both the vehicle and MP controls. fCNTs significantly increased the presence of morphological defects, resorptions and skeletal abnormalities in CD-1 mice, but had little effect on Drosophila. We speculate that the differences seen in the effects of NP types may be partially due to differences in reproductive physiology as well as each organism's ability to internalize these NPs. Whereas the differing response of each organism to a NP type was likely due in part to

  2. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

    Directory of Open Access Journals (Sweden)

    Bello Bruno C

    2008-02-01

    Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  3. Early prosocial development across cultures.

    Science.gov (United States)

    Callaghan, Tara; Corbit, John

    2017-08-17

    Human prosociality is ubiquitous, even though it may be manifested differently across cultures. Low cost helping and sharing emerge early in development, and at similar levels, across cultures having vastly different sociocultural niches. Developmental trajectories for costly sharing diverge across cultures around middle childhood, in line with differences in the sociocultural niches that children experience. Cultural developmental research has focussed primarily on the emergence and development of prosocial behaviour, and would benefit from an examination of the interplay between psychological (cognitive, motivational) and sociocultural (norms, developmental niche) foundations over ontogeny. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling.

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    Yu-Chen Tsai

    Full Text Available Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired.

  5. Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling.

    Science.gov (United States)

    Tsai, Yu-Chen; Grimm, Stefan; Chao, Ju-Lan; Wang, Shih-Chin; Hofmeyer, Kerstin; Shen, Jie; Eichinger, Fred; Michalopoulou, Theoni; Yao, Chi-Kuang; Chang, Chih-Hsuan; Lin, Shih-Han; Sun, Y Henry; Pflugfelder, Gert O

    2015-01-01

    Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired.

  6. Preferential genome targeting of the CBP co-activator by Rel and Smad proteins in early Drosophila melanogaster embryos.

    Directory of Open Access Journals (Sweden)

    Per-Henrik Holmqvist

    Full Text Available CBP and the related p300 protein are widely used transcriptional co-activators in metazoans that interact with multiple transcription factors. Whether CBP/p300 occupies the genome equally with all factors or preferentially binds together with some factors is not known. We therefore compared Drosophila melanogaster CBP (nejire ChIP-seq peaks with regions bound by 40 different transcription factors in early embryos, and we found high co-occupancy with the Rel-family protein Dorsal. Dorsal is required for CBP occupancy in the embryo, but only at regions where few other factors are present. CBP peaks in mutant embryos lacking nuclear Dorsal are best correlated with TGF-ß/Dpp-signaling and Smad-protein binding. Differences in CBP occupancy in mutant embryos reflect gene expression changes genome-wide, but CBP also occupies some non-expressed genes. The presence of CBP at silent genes does not result in histone acetylation. We find that Polycomb-repressed H3K27me3 chromatin does not preclude CBP binding, but restricts histone acetylation at CBP-bound genomic sites. We conclude that CBP occupancy in Drosophila embryos preferentially overlaps factors controlling dorso-ventral patterning and that CBP binds silent genes without causing histone hyperacetylation.

  7. Preferential Genome Targeting of the CBP Co-Activator by Rel and Smad Proteins in Early Drosophila melanogaster Embryos

    Science.gov (United States)

    Holmqvist, Per-Henrik; Boija, Ann; Philip, Philge; Crona, Filip; Stenberg, Per; Mannervik, Mattias

    2012-01-01

    CBP and the related p300 protein are widely used transcriptional co-activators in metazoans that interact with multiple transcription factors. Whether CBP/p300 occupies the genome equally with all factors or preferentially binds together with some factors is not known. We therefore compared Drosophila melanogaster CBP (nejire) ChIP–seq peaks with regions bound by 40 different transcription factors in early embryos, and we found high co-occupancy with the Rel-family protein Dorsal. Dorsal is required for CBP occupancy in the embryo, but only at regions where few other factors are present. CBP peaks in mutant embryos lacking nuclear Dorsal are best correlated with TGF-ß/Dpp-signaling and Smad-protein binding. Differences in CBP occupancy in mutant embryos reflect gene expression changes genome-wide, but CBP also occupies some non-expressed genes. The presence of CBP at silent genes does not result in histone acetylation. We find that Polycomb-repressed H3K27me3 chromatin does not preclude CBP binding, but restricts histone acetylation at CBP-bound genomic sites. We conclude that CBP occupancy in Drosophila embryos preferentially overlaps factors controlling dorso-ventral patterning and that CBP binds silent genes without causing histone hyperacetylation. PMID:22737084

  8. A rapid, membrane-dependent pathway directs furrow formation through RalA in the early Drosophila embryo.

    Science.gov (United States)

    Holly, Ryan M; Mavor, Lauren M; Zuo, Zhongyuan; Blankenship, J Todd

    2015-07-01

    Plasma membrane furrow formation is crucial in cell division and cytokinesis. Furrow formation in early syncytial Drosophila embryos is exceptionally rapid, with furrows forming in as little as 3.75 min. Here, we use 4D imaging to identify furrow formation, stabilization, and regression periods, and identify a rapid, membrane-dependent pathway that is essential for plasma membrane furrow formation in vivo. Myosin II function is thought to provide the ingression force for cytokinetic furrows, but the role of membrane trafficking pathways in guiding furrow formation is less clear. We demonstrate that a membrane trafficking pathway centered on Ras-like protein A (RalA) is required for fast furrow ingression in the early fly embryo. RalA function is absolutely required for furrow formation and initiation. In the absence of RalA and furrow function, chromosomal segregation is aberrant and polyploid nuclei are observed. RalA localizes to syncytial furrows, and mediates the movement of exocytic vesicles to the plasma membrane. Sec5, which is an exocyst complex subunit and localizes to ingressing furrows in wild-type embryos, becomes punctate and loses its cortical association in the absence of RalA function. Rab8 also fails to traffic to the plasma membrane and accumulates aberrantly in the cytoplasm in RalA disrupted embryos. RalA localization precedes F-actin recruitment to the furrow tip, suggesting that membrane trafficking might function upstream of cytoskeletal remodeling. These studies identify a pathway, which stretches from Rab8 to RalA and the exocyst complex, that mediates rapid furrow formation in early Drosophila embryos.

  9. Parental exposure to low-dose X-rays in Drosophila melanogaster induces early emergence in offspring, which can be modulated by transplantation of polar cytoplasm

    Energy Technology Data Exchange (ETDEWEB)

    Kanao, Tomoko; Okamoto, Takehito; Miyachi, Yukihisa; Nohara, Norimasa

    2003-06-19

    In recent years there has been growing concern over the biological effects of low-dose X-rays, but few studies have addressed this issue. Our laboratory had observed flies (Drosophila melanogaster) irradiated with low-dose X-rays tend to emerge earlier than normal flies. This observation led us to quantitatively examine the effects of low-dose X-irradiation on development in the fly. Following exposure of prepupal (day 5) flies to 0.5 Gy X-rays, the time to emergence was slightly shorter than in the sham controls. This tendency was increased when the X-ray exposure came during the pupal stage (day 7). In these flies, the time to eclosion decreased significantly, by an average of 30 h sooner than sham controls. A further experiment examined whether such radiation effects could be observed in the unexposed F1 generation of exposed individuals. Greater radiation effects on early F1 emergence were seen when the time between exposure and mating was 3 days, indicating an effect on early spermatid development. Early F1 emergence was also observed after exposure of female flies to X-rays during late previtellogeny. Furthermore, rapid emergence could be induced in the F1 embryos of unexposed parents by transferring the polar cytoplasm (precursor cells of the germ cell line) from F1 embryos of exposed flies. These results show that radiation-induced effects can be transmitted to the next generation through the germ cell line.

  10. Smurf-mediated differential proteolysis generates dynamic BMP signaling in germline stem cells during Drosophila testis development.

    Science.gov (United States)

    Chang, Yi-Jie; Pi, Haiwei; Hsieh, Chang-Che; Fuller, Margaret T

    2013-11-01

    Germline stem cells (GSCs) produce gametes throughout the reproductive life of many animals, and intensive studies have revealed critical roles of BMP signaling to maintain GSC self-renewal in Drospophila adult gonads. Here, we show that BMP signaling is downregulated as testes develop and this regulation controls testis growth, stem cell number, and the number of spermatogonia divisions. Phosphorylated Mad (pMad), the activated Drosophila Smad in germ cells, was restricted from anterior germ cells to GSCs and hub-proximal cells during early larval development. pMad levels in GSCs were then dramatically downregulated from early third larval instar (L3) to late L3, and maintained at low levels in pupal and adult GSCs. The spatial restriction and temporal down-regulation of pMad, reflecting the germ cell response to BMP signaling activity, required action in germ cells of E3 ligase activity of HECT domain protein Smurf. Analyses of Smurf mutant testes and dosage-dependent genetic interaction between Smurf and mad indicated that pMad downregulation was required for both the normal decrease in stem cell number during testis maturation in the pupal stage, and for normal limit of four rounds of spermatogonia cell division for control of germ cell numbers and testis size. Smurf protein was expressed at a constant low level in GSCs and spermatogonia during development. Rescue experiments showed that expression of exogenous Smurf protein in early germ cells promoted pMad downregulation in GSCs in a stage-dependent but concentration-independent manner, suggesting that the competence of Smurf to attenuate response to BMP signaling may be regulated during development. Taken together, our work reveals a critical role for differential attenuation of the response to BMP signaling in GSCs and early germ cells for control of germ cell number and gonad growth during development.

  11. Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster

    Indian Academy of Sciences (India)

    Heinrich Reichert

    2014-09-01

    Groundbreaking work by Obaid Siddiqi has contributed to the powerful genetic toolkit that is now available for studying the nervous system of Drosophila. Studies carried out in this powerful neurogenetic model system during the last decade now provide insight into the molecular mechanisms that operate in neural stem cells during normal brain development and during abnormal brain tumorigenesis. These studies also provide strong support for the notion that conserved molecular genetic programs act in brain development and disease in insects and mammals including humans.

  12. Myelopoiesis during Zebrafish Early Development

    Institute of Scientific and Technical Information of China (English)

    Jin Xu; Linsen Du; Zilong Wen

    2012-01-01

    Myelopoiesis is the process of producing all types of myeloid cells including monocytes/macrophages and granulocytes.Myeloid cells are known to manifest a wide spectrum of activities such as immune surveillance and tissue remodeling.Irregularities in myeloid cell development and their function are known to associate with the onset and the progression of a variety of human disorders such as leukemia.In the past decades,extensive studies have been carried out in various model organisms to elucidate the molecular mechanisms underlying myelopoiesis with the hope that these efforts will yield knowledge translatable into therapies for related diseases.Zebrafish has recently emerged as a prominent animal model for studying myelopoiesis,especially during early embryogenesis,largely owing to its unique properties such as transparent embryonic body and external development.This review introduces the methodologies used in zebrafish research and focuses on the recent research progresses of zebrafish myelopoiesis.

  13. CREB Binding Protein Functions During Successive Stages of Eye Development in Drosophila

    Science.gov (United States)

    Kumar, Justin P.; Jamal, Tazeen; Doetsch, Alex; Turner, F. Rudolf; Duffy, Joseph B.

    2004-01-01

    During the development of the compound eye of Drosophila several signaling pathways exert both positive and inhibitory influences upon an array of nuclear transcription factors to produce a near-perfect lattice of unit eyes or ommatidia. Individual cells within the eye are exposed to many extracellular signals, express multiple surface receptors, and make use of a large complement of cell-subtype-specific DNA-binding transcription factors. Despite this enormous complexity, each cell will make the correct developmental choice and adopt the appropriate cell fate. How this process is managed remains a poorly understood paradigm. Members of the CREB binding protein (CBP)/p300 family have been shown to influence development by (1) acting as bridging molecules between the basal transcriptional machinery and specific DNA-binding transcription factors, (2) physically interacting with terminal members of signaling cascades, (3) acting as transcriptional coactivators of downstream target genes, and (4) playing a key role in chromatin remodeling. In a screen for new genes involved in eye development we have identified the Drosophila homolog of CBP as a key player in both eye specification and cell fate determination. We have used a variety of approaches to define the role of CBP in eye development on a cell-by-cell basis. PMID:15514061

  14. A gene expression atlas of a bicoid-depleted Drosophila embryo reveals early canalization of cell fate.

    Science.gov (United States)

    Staller, Max V; Fowlkes, Charless C; Bragdon, Meghan D J; Wunderlich, Zeba; Estrada, Javier; DePace, Angela H

    2015-02-01

    In developing embryos, gene regulatory networks drive cells towards discrete terminal fates, a process called canalization. We studied the behavior of the anterior-posterior segmentation network in Drosophila melanogaster embryos by depleting a key maternal input, bicoid (bcd), and measuring gene expression patterns of the network at cellular resolution. This method results in a gene expression atlas containing the levels of mRNA or protein expression of 13 core patterning genes over six time points for every cell of the blastoderm embryo. This is the first cellular resolution dataset of a genetically perturbed Drosophila embryo that captures all cells in 3D. We describe the technical developments required to build this atlas and how the method can be employed and extended by others. We also analyze this novel dataset to characterize the degree and timing of cell fate canalization in the segmentation network. We find that in two layers of this gene regulatory network, following depletion of bcd, individual cells rapidly canalize towards normal cell fates. This result supports the hypothesis that the segmentation network directly canalizes cell fate, rather than an alternative hypothesis whereby cells are initially mis-specified and later eliminated by apoptosis. Our gene expression atlas provides a high resolution picture of a classic perturbation and will enable further computational modeling of canalization and gene regulation in this transcriptional network. © 2015. Published by The Company of Biologists Ltd.

  15. Expression of COPI components during development of Drosophila melanogaster.

    Science.gov (United States)

    Grieder, Nicole C; Kloter, Urs; Gehring, Walter J

    2005-12-01

    In a P{lArB} enhancer detector collection, a line was found that showed upregulated expression within centrally to posteriorly located germarial cysts. It was inserted in the gammaCOP locus on chromosome 3R. GammaCOP is a component of the COPI coatomer involved in membrane traffic. Most of the other known components of the COPI coatomer also showed higher expression in the posterior half of the germarium. Not only meiotic germline cysts but also migrating follicle cells upregulate the COPI subunits. During embryonic and larval development, the COPI subunits are expressed ubiquitously as expected for genes required for cell viability. In addition, they are strongly expressed in the salivary glands and the proventriculus. Whether tissue-specific transcriptional upregulation of COPI subunits is required for the reorganization of membranous compartments that are needed for the developmental processes that confer cyst polarity and follicle maturation will have to be addressed in a genetic study.

  16. Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development

    Science.gov (United States)

    Norga, Koenraad K.; Gurganus, Marjorie C.; Dilda, Christy L.; Yamamoto, Akihiko; Lyman, Richard F.; Patel, Prajal H.; Rubin, Gerald M.; Hoskins, Roger A.; Mackay, Trudy F.; Bellen, Hugo J.

    2003-01-01

    BACKGROUND: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation. RESULTS: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci. CONCLUSIONS: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.

  17. Mitochondrial electron transport chain dysfunction during development does not extend lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Rera, Michael; Monnier, Véronique; Tricoire, Hervé

    2010-02-01

    Since the initial identification of reactive oxygen species (ROS) as the major factor in aging, many studies have provided evidence for the central role of mitochondria in longevity. A few years ago, an unexpected finding showed that the inactivation of the mitochondrial respiratory chain (MRC) in Caenorhabditis elegans, during the developmental stages only, extended lifespan. Activation of this mitochondrial pathway affecting aging (MIT) is associated with several phenotypic features: increased longevity, increased time of development, decreased fertility/fecundity and reduced adult size. Here, we investigated this pathway in another model organism, Drosophila melanogaster. To assess the role of mitochondrial activity in the Drosophila aging process, we partially inactivated the MRC using RNA interference (RNAi) during larval stages. Developmental perturbation of the respiratory process prolonged development, increased lethality during developmental stage, reduced both fecundity and fertility and slightly reduced individual weight. However, in contrast to the nematode, this genetic intervention either shortened or had no effect on lifespan, depending on the level of gene inactivation. Thus, the effects of MRC disruption during development on aging differ between species. We discuss the possible origins of such differences.

  18. Stable Binding of the Conserved Transcription Factor Grainy Head to its Target Genes Throughout Drosophila melanogaster Development.

    Science.gov (United States)

    Nevil, Markus; Bondra, Eliana R; Schulz, Katharine N; Kaplan, Tommy; Harrison, Melissa M

    2017-02-01

    It has been suggested that transcription factor binding is temporally dynamic, and that changes in binding determine transcriptional output. Nonetheless, this model is based on relatively few examples in which transcription factor binding has been assayed at multiple developmental stages. The essential transcription factor Grainy head (Grh) is conserved from fungi to humans, and controls epithelial development and barrier formation in numerous tissues. Drosophila melanogaster, which possess a single grainy head (grh) gene, provide an excellent system to study this conserved factor. To determine whether temporally distinct binding events allow Grh to control cell fate specification in different tissue types, we used a combination of ChIP-seq and RNA-seq to elucidate the gene regulatory network controlled by Grh during four stages of embryonic development (spanning stages 5-17) and in larval tissue. Contrary to expectations, we discovered that Grh remains bound to at least 1146 genomic loci over days of development. In contrast to this stable DNA occupancy, the subset of genes whose expression is regulated by Grh varies. Grh transitions from functioning primarily as a transcriptional repressor early in development to functioning predominantly as an activator later. Our data reveal that Grh binds to target genes well before the Grh-dependent transcriptional program commences, suggesting it sets the stage for subsequent recruitment of additional factors that execute stage-specific Grh functions. Copyright © 2017 by the Genetics Society of America.

  19. A toxicity assessment of hydroxyapatite nanoparticles on development and behaviour of Drosophila melanogaster

    Science.gov (United States)

    Pappus, S. Aurosman; Ekka, Basanti; Sahu, Swetapadma; Sabat, Debabrat; Dash, Priyabrat; Mishra, Monalisa

    2017-04-01

    The effects of oral intake of hydroxyapatite nanoparticles (HApNPs) were investigated on growth, development and behaviour of Drosophila. The Drosophila responses to various concentrations of HApNPs were compared. At lower concentrations, i.e. 5 mg L-1 more amount of oxidative stress was produced than that of highest concentration, i.e. 80 mg L-1. The increased amounts of oxidative stress reflect a higher amount of ROS production and increased cell damage within the larval gut. HApNPs was further shown to interfere with the calcium and phosphorus absorption pathway. Besides all these damage, HApNPs causes developmental delay in the late third instar larvae. The most significant anomaly was observed in pupae count, fly hatching after the feeding of HApNPs. Flies hatched from treated vials have decreased body weight with defective walking behaviour. Hatched flies have a phenotypic defect in the wing, eye and thorax of the bristles. Along with these changes, the adult fly becomes more prone towards stress. The findings hint that HApNPs persuade noxious effects and alter the development, structure, function and behaviour of the fly in a concentration-dependent manner.

  20. Myosin VI contributes to synaptic transmission and development at the Drosophila neuromuscular junction

    Directory of Open Access Journals (Sweden)

    Campbell Shelagh

    2011-07-01

    Full Text Available Abstract Background Myosin VI, encoded by jaguar (jar in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. Myosin VI is the only myosin known to move towards the minus or pointed ends of actin filaments. Although Myosin VI has been implicated in numerous cellular processes as both an anchor and a transporter, little is known about the role of Myosin VI in the nervous system. We previously recovered jar in a screen for genes that modify neuromuscular junction (NMJ development and here we report on the genetic analysis of Myosin VI in synaptic development and function using loss of function jar alleles. Results Our experiments on Drosophila third instar larvae revealed decreased locomotor activity, a decrease in NMJ length, a reduction in synaptic bouton number, and altered synaptic vesicle localization in jar mutants. Furthermore, our studies of synaptic transmission revealed alterations in both basal synaptic transmission and short-term plasticity at the jar mutant neuromuscular synapse. Conclusions Altogether these findings indicate that Myosin VI is important for proper synaptic function and morphology. Myosin VI may be functioning as an anchor to tether vesicles to the bouton periphery and, thereby, participating in the regulation of synaptic vesicle mobilization during synaptic transmission.

  1. ATM is required for telomere maintenance and chromosome stability during Drosophila development.

    Science.gov (United States)

    Silva, Elizabeth; Tiong, Stanley; Pedersen, Michael; Homola, Ellen; Royou, Anne; Fasulo, Barbara; Siriaco, Giorgia; Campbell, Shelagh D

    2004-08-10

    ATM is a large, multifunctional protein kinase that regulates responses required for surviving DNA damage: including DNA repair, apoptosis, and cell cycle checkpoints. Here, we show that Drosophila ATM function is essential for normal adult development. Extensive, inappropriate apoptosis occurs in proliferating atm mutant tissues, and in clonally derived atm mutant embryos, frequent mitotic defects were seen. At a cellular level, spontaneous telomere fusions and other chromosomal abnormalities are common in atm larval neuroblasts, suggesting a conserved and essential role for dATM in the maintenance of normal telomeres and chromosome stability. Evidence from other systems supports the idea that DNA double-strand break (DSB) repair functions of ATM kinases promote telomere maintenance by inhibition of illegitimate recombination or fusion events between the legitimate ends of chromosomes and spontaneous DSBs. Drosophila will be an excellent model system for investigating how these ATM-dependent chromosome structural maintenance functions are deployed during development. Because neurons appear to be particularly sensitive to loss of ATM in both flies and humans, this system should be particularly useful for identifying cell-specific factors that influence sensitivity to loss of dATM and are relevant for understanding the human disease, ataxia-telangiectasia.

  2. Parental exposure to low-dose X-rays in Drosophila melanogaster induces early emergence offspring, which can be modulated by transplantation of polar cytoplasm

    Energy Technology Data Exchange (ETDEWEB)

    Kanao, T.; Okamoto, T.; Miyachi, Y.

    2004-07-01

    In recent years there has been growing concern over the biological effects of low-dose X-rays, but few studies have addressed this issue. Our laboratory had observed files (Drosophila melanogaster) irradiated with low dose X-rays tend to emerge earlier than normal flies. This observation led us to quantitatively examine the effects of low dose X-irradiation on development in the fly Following exposure of prepupal (day 5) flies to 0.5 Gy X-rays, the time to emergence was slightly shorter than in the sham controls. This tendency was increased when the X-ray exposure came during the pupal stage (day 7). In these flies, the time to eclosion decreased significantly, by an average of thirty hours sooner than sham controls. Exposure of pre pupa to 0.5 Gy results in marked changes in the puffing patterns of salivary gland chromosomes. A 0.5 Gy exposure induces puffing at 75B specific loci; this pattern of induced puffs shows little developmental specificity. A further experiment examined whether such radiation effects could be observed in the unexposed F1 generation of exposed individuals Greater radiation effects on early Fi emergence were seen when the time between exposure and mating was 3 days, indicating an effect on early spermatid development. Early F1 emergence was also observed after exposure of female flies to X-rays during late previtellogeny. furthermore, rapid emergence could be induced in the F1 embryos of unexposed parents by transferring the polar cytoplasm (precursor cells of the germ cell line) from F1 embryos of exposed flies. furthermore pumilio mutant arrested the assembly of polar cytoplasm did not induce the early emergency even after 0.5 Gy exposure. These results show that radiation-induced effects can be transmitted to the next generation through the germ cell line. (Author)

  3. The endo-siRNA pathway is essential for robust development of the Drosophila embryo.

    Directory of Open Access Journals (Sweden)

    Elena M Lucchetta

    Full Text Available BACKGROUND: Robustness to natural temperature fluctuations is critical to proper development in embryos and to cellular functions in adult organisms. However, mechanisms and pathways which govern temperature compensation remain largely unknown beyond circadian rhythms. Pathways which ensure robustness against temperature fluctuations may appear to be nonessential under favorable, uniform environmental conditions used in conventional laboratory experiments where there is little variation for which to compensate. The endo-siRNA pathway, which produces small double-stranded RNAs in Drosophila, appears to be nonessential for robust development of the embryo under ambient uniform temperature and to be necessary only for viral defense. Embryos lacking a functional endo-siRNA pathway develop into phenotypically normal adults. However, we hypothesized that small RNAs may regulate the embryo's response to temperature, as a ribonucleoprotein complex has been previously shown to mediate mammalian cell response to heat shock. PRINCIPAL FINDINGS: Here, we show that the genes DICER-2 and ARGONAUTE2, which code for integral protein components of the endo-siRNA pathway, are essential for robust development and temperature compensation in the Drosophila embryo when exposed to temperature perturbations. The regulatory functions of DICER-2 and ARGONAUTE2 were uncovered by using microfluidics to expose developing Drosophila embryos to a temperature step, in which each half of the embryo develops at a different temperature through developmental cycle 14. Under this temperature perturbation, dicer-2 or argonaute2 embryos displayed abnormal segmentation. The abnormalities in segmentation are presumably due to the inability of the embryo to compensate for temperature-induced differences in rate of development and to coordinate developmental timing in the anterior and posterior halves. A deregulation of the length of nuclear division cycles 10-14 is also observed in

  4. Drosophila cyfip regulates synaptic development and endocytosis by suppressing filamentous actin assembly.

    Science.gov (United States)

    Zhao, Lu; Wang, Dan; Wang, Qifu; Rodal, Avital A; Zhang, Yong Q

    2013-04-01

    The formation of synapses and the proper construction of neural circuits depend on signaling pathways that regulate cytoskeletal structure and dynamics. After the mutual recognition of a growing axon and its target, multiple signaling pathways are activated that regulate cytoskeletal dynamics to determine the morphology and strength of the connection. By analyzing Drosophila mutations in the cytoplasmic FMRP interacting protein Cyfip, we demonstrate that this component of the WAVE complex inhibits the assembly of filamentous actin (F-actin) and thereby regulates key aspects of synaptogenesis. Cyfip regulates the distribution of F-actin filaments in presynaptic neuromuscular junction (NMJ) terminals. At cyfip mutant NMJs, F-actin assembly was accelerated, resulting in shorter NMJs, more numerous satellite boutons, and reduced quantal content. Increased synaptic vesicle size and failure to maintain excitatory junctional potential amplitudes under high-frequency stimulation in cyfip mutants indicated an endocytic defect. cyfip mutants exhibited upregulated bone morphogenetic protein (BMP) signaling, a major growth-promoting pathway known to be attenuated by endocytosis at the Drosophila NMJ. We propose that Cyfip regulates synapse development and endocytosis by inhibiting actin assembly.

  5. FGF signaling supports Drosophila fertility by regulating development of ovarian muscle tissues.

    Science.gov (United States)

    Irizarry, Jihyun; Stathopoulos, Angelike

    2015-08-01

    The thisbe (ths) gene encodes a Drosophila fibroblast growth factor (FGF), and mutant females are viable but sterile suggesting a link between FGF signaling and fertility. Ovaries exhibit abnormal morphology including lack of epithelial sheaths and muscle tissues that surround ovarioles. Here we investigated how FGF influences Drosophila ovary morphogenesis and identified several roles. Heartless (Htl) FGF receptor was found to be expressed within somatic cells at the larval and pupal stages, and phenotypes were uncovered using RNAi. Differentiation of terminal filament cells was affected, but this effect did not alter the ovariole number. In addition, proliferation of epithelial sheath progenitors, the apical cells, was decreased in both htl and ths mutants, while ectopic expression of the Ths ligand led to these cells' over-proliferation suggesting that FGF signaling supports ovarian muscle sheath formation by controlling apical cell number in the developing gonad. Additionally, live imaging of adult ovaries was used to show that htl RNAi mutants, hypomorphic mutants in which epithelial sheaths are present, exhibit abnormal muscle contractions. Collectively, our results demonstrate that proper formation of ovarian muscle tissues is regulated by FGF signaling in the larval and pupal stages through control of apical cell proliferation and is required to support fertility.

  6. Drosophila DOCK family protein sponge regulates the JNK pathway during thorax development.

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    Morishita, Kazushige; Ozasa, Fumito; Eguchi, Koichi; Yoshioka, Yasuhide; Yoshida, Hideki; Hiai, Hiroshi; Yamaguchi, Masamitsu

    2014-01-01

    The dedicator of cytokinesis (DOCK) family proteins that are conserved in a wide variety of species are known as DOCK1-DOCK11 in mammals. The Sponge (Spg) is a Drosophila counterpart to the mammalian DOCK3. Specific knockdown of spg by pannir-GAL4 or apterous-GAL4 driver in wing discs induced split thorax phenotype in adults. Reduction of the Drosophila c-Jun N-terminal kinase (JNK), basket (bsk) gene dose enhanced the spg knockdown-induced phenotype. Conversely, overexpression of bsk suppressed the split thorax phenotype. Monitoring JNK activity in the wing imaginal discs by immunostaining with anti-phosphorylated JNK (anti-pJNK) antibody together with examination of lacZ expression in a puckered-lacZ enhancer trap line revealed the strong reduction of the JNK activity in the spg knockdown clones. This was further confirmed by Western immunoblot analysis of extracts from wing discs of spg knockdown fly with anti-pJNK antibody. Furthermore, the Duolink in situ Proximity Ligation Assay method detected interaction signals between Spg and Rac1 in the wing discs. Taken together, these results indicate Spg positively regulates JNK pathway that is required for thorax development and the regulation is mediated by interaction with Rac1.

  7. From Drosophila development to adult: clues to Notch function in long-term memory

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    Jiabin eZhang

    2013-11-01

    Full Text Available Notch is a cell surface receptor that is well known to mediate inter-cellular communication during animal development. Data in the field indicate that it is also involved in the formation of long-term memory (LTM in the fully developed adults and in memory loss upon neurodegeneration. Our studies in the model organism Drosophila reveal that a non-canonical Notch-Protein Kinase C (PKC activity that plays critical roles in embryonic development also regulates Cyclic-AMP Response Element Binding protein (CREB during LTM formation in adults. Here we present a perspective on how the various known features of Notch function relate to LTM formation and how they might interface with elements of Wingless/Wnt signaling in this process.

  8. Muscle organizers in Drosophila: the role of persistent larval fibers in adult flight muscle development

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    Farrell, E. R.; Fernandes, J.; Keshishian, H.

    1996-01-01

    In many organisms muscle formation depends on specialized cells that prefigure the pattern of the musculature and serve as templates for myoblast organization and fusion. These include muscle pioneers in insects and muscle organizing cells in leech. In Drosophila, muscle founder cells have been proposed to play a similar role in organizing larval muscle development during embryogenesis. During metamorphosis in Drosophila, following histolysis of most of the larval musculature, there is a second round of myogenesis that gives rise to the adult muscles. It is not known whether muscle founder cells organize the development of these muscles. However, in the thorax specific larval muscle fibers do not histolyze at the onset of metamorphosis, but instead serve as templates for the formation of a subset of adult muscles, the dorsal longitudinal flight muscles (DLMs). Because these persistent larval muscle fibers appear to be functioning in many respects like muscle founder cells, we investigated whether they were necessary for DLM development by using a microbeam laser to ablate them singly and in combination. We found that, in the absence of the larval muscle fibers, DLMs nonetheless develop. Our results show that the persistent larval muscle fibers are not required to initiate myoblast fusion, to determine DLM identity, to locate the DLMs in the thorax, or to specify the total DLM fiber volume. However, they are required to regulate the number of DLM fibers generated. Thus, while the persistent larval muscle fibers are not obligatory for DLM fiber formation and differentiation, they are necessary to ensure the development of the correct number of fibers.

  9. [THE ROLE OF sbr/Dm nxf1 GENE DURING SYNCYTIAL PERIODS OF DEVELOPMENT IN DROSOPHILA MELANOGASTER].

    Science.gov (United States)

    Golubkova, E V; Atsapkina, A A; Mamon, L A

    2015-01-01

    The syncytial development is a feature of early embryogenesis and spermatogenesis in Drosophila melanogaster. All elements of syncytium are interconnected by single cytoskeletal network that enables equal conditions and provides synchronic development. The cytoskeleton is essential for the formation and functioning of the mitotic spindle, cytoskeletal elements are the main structural component of cilia and flagella. Intra- and intercellular transport, morphogenesis processes depend from cytoskeleton on both within a single cell, and at the level of the whole organism. The sbr (small bristles) gene of D. melanogaster belongs to the NXF (nuclear export factor) evolutionarily conservative proteins family. Gene Dm nxf1 (sbr), as well as its orthologs in other organisms, controls the export of poly(A)-containing RNA from the nucleus to the cytoplasm, and the corresponding proteins are usually localized in the nucleus or in the nuclear envelope. For SBR protein we have shown the localization not only in the nucleus, but in the cytoplasm marking of characteristic cytoplasmic structures. A breach of the cytoskeleton in the sbr (Dm nxf1) mutant in D. melanogaster shown by us and cytoplasmic localization of the protein SBR allow us to link the specific functions of this protein with the dynamics of the cytoskeleton.

  10. Live imaging of epidermal morphogenesis during the development of the adult abdominal epidermis of Drosophila.

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    Ninov, Nikolay; Martín-Blanco, Enrique

    2007-01-01

    During larval stages of Drosophila development, the abdominal epidermis is composed of histoblasts (adult precursors) and larval epidermal cells (LECs). During metamorphosis, histoblasts proliferate and colonize the territories occupied by the LECs, which die and become engulfed by macrophages. This morphogenetic process is an excellent model for in vivo analysis of epithelial migration, cell division, cell death, patterning and differentiation. Here, we describe a protocol for time-lapse recording of the developing epidermis during metamorphosis. The protocol describes the removal of the pupal case (which acts as an opaque barrier to effective imaging) and mounting and imaging of specimens of different stages so that normal developmental processes are preserved. This method enables high-resolution studies over long time periods using fluorescent markers and confocal microscopy. The protocol requires 1 h for pupal dissection and mounting and, depending on the stages and genotypes to be analyzed, several more hours for preprocessing and aging and developmental staging of flies and pupae.

  11. INFLUENCE OF AMYLOSE STARCH ON DEVELOPMENT AND LIFESPAN OF FRUIT FLY DROSOPHILA MELANOGASTER

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    Oleksandra Abrat

    2015-05-01

    Full Text Available Last years, the concept of resistant starch (RS has evoked a new interest in researchers in the context of bioavailability of starch and its use as a source of dietary fiber. Based on clinical and animal research, RS has been proposed to be the most potentially beneficial starch fraction for human health. In this study, the effects of amylose starch as a fraction of RS on development and lifespan of fruit fly Drosophila melanogaster were investigated. In both Canton S and w1118 strains, the diet with 20% amylose RS delayed fly development, increased triacylglyceride level in the body of adult insects and reduced their lifespan compared to the diet with 4% amylose starch. Thus, our data clearly demonstrate that amylose starch at high concentrations may negatively affect fruit fly.

  12. Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila

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    Nolo, R.; Abbott, L. A.; Bellen, H. J.

    2000-01-01

    The senseless (sens) gene is required for proper development of most cell types of the embryonic and adult peripheral nervous system (PNS) of Drosophila. Sens is a nuclear protein with four Zn fingers that is expressed and required in the sensory organ precursors (SOP) for proper proneural gene expression. Ectopic expression of Sens in many ectodermal cells causes induction of PNS external sensory organ formation and is able to recreate an ectopic proneural field. Hence, sens is both necessary and sufficient for PNS development. Our data indicate that proneural genes activate sens expression. Sens is then in turn required to further activate and maintain proneural gene expression. This feedback mechanism is essential for selective enhancement and maintenance of proneural gene expression in the SOPs.

  13. Six3, a medaka homologue of the Drosophila homeobox gene sine oculis is expressed in the anterior embryonic shield and the developing eye.

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    Loosli, F; Köster, R W; Carl, M; Krone, A; Wittbrodt, J

    1998-06-01

    homologue Six3 (Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). sine oculis (so) is essential for the development of the larval and adult visual system (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron l2, 977-996). Six3 is expressed in the anterior neural plate and optic vesicles, lens, olfactory placodes and ventral forebrain (Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). Overexpression of mouse Six3 gene in medaka fish embryos (Orvzias latipes) results in the formation of an ectopic lens, indicating that Six3 activity can trigger the genetic pathway leading to lens formation (Oliver, G., Loosli, F., Koster, R., Wittbrodt, J., Gruss, P., 1996. Ectopic lens induction in fish in response to the murine homeobox gene Six3. Mech. Dev. 60, 233-239). We isolated the medaka Six3 homologue and analyzed its expression pattern in the medaka embryo. It is expressed initially in the anterior embryonic shield and later in the developing eye and prosencephalon. The early localized expression of Six3 suggests a role in the regionalization of the rostral head.

  14. Class I myosins have overlapping and specialized functions in left-right asymmetric development in Drosophila.

    Science.gov (United States)

    Okumura, Takashi; Sasamura, Takeshi; Inatomi, Momoko; Hozumi, Shunya; Nakamura, Mitsutoshi; Hatori, Ryo; Taniguchi, Kiichiro; Nakazawa, Naotaka; Suzuki, Emiko; Maeda, Reo; Yamakawa, Tomoko; Matsuno, Kenji

    2015-04-01

    The class I myosin genes are conserved in diverse organisms, and their gene products are involved in actin dynamics, endocytosis, and signal transduction. Drosophila melanogaster has three class I myosin genes, Myosin 31DF (Myo31DF), Myosin 61F (Myo61F), and Myosin 95E (Myo95E). Myo31DF, Myo61F, and Myo95E belong to the Myosin ID, Myosin IC, and Myosin IB families, respectively. Previous loss-of-function analyses of Myo31DF and Myo61F revealed important roles in left-right (LR) asymmetric development and enterocyte maintenance, respectively. However, it was difficult to elucidate their roles in vivo, because of potential redundant activities. Here we generated class I myosin double and triple mutants to address this issue. We found that the triple mutant was viable and fertile, indicating that all three class I myosins were dispensable for survival. A loss-of-function analysis revealed further that Myo31DF and Myo61F, but not Myo95E, had redundant functions in promoting the dextral LR asymmetric development of the male genitalia. Myo61F overexpression is known to antagonize the dextral activity of Myo31DF in various Drosophila organs. Thus, the LR-reversing activity of overexpressed Myo61F may not reflect its physiological function. The endogenous activity of Myo61F in promoting dextral LR asymmetric development was observed in the male genitalia, but not the embryonic gut, another LR asymmetric organ. Thus, Myo61F and Myo31DF, but not Myo95E, play tissue-specific, redundant roles in LR asymmetric development. Our studies also revealed differential colocalization of the class I myosins with filamentous (F)-actin in the brush border of intestinal enterocytes. Copyright © 2015 by the Genetics Society of America.

  15. Empty spiracles is required for the development of olfactory projection neuron circuitry in Drosophila.

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    Lichtneckert, Robert; Nobs, Lionel; Reichert, Heinrich

    2008-08-01

    In both insects and mammals, second-order olfactory neurons receive input from olfactory receptor neurons and relay olfactory input to higher brain centers. In Drosophila, the wiring specificity of these olfactory projection neurons (PNs) is predetermined by their lineage identity and birth order. However, the genetic programs that control this wiring specificity are not well understood. The cephalic gap gene empty spiracles (ems) encodes a homeodomain transcription factor required for embryonic development of the antennal brain neuromere. Here we show that ems is expressed postembryonically in the progenitors of the two major olfactory PN lineages. Moreover, we show that ems has cell lineage-specific functions in postembryonic PN development. Thus, in the lateral PN lineage, transient ems expression is essential for development of the correct number of PNs; in ems mutants, the number of PNs in the lineage is dramatically reduced by apoptosis. By contrast, in the anterodorsal PN lineage, transient ems expression is necessary for precise targeting of PN dendrites to appropriate glomeruli; in ems mutants, these PNs fail to innervate correct glomeruli, innervate inappropriate glomeruli, or mistarget dendrites to other brain regions. Furthermore, in the anterodorsal PN lineage, ems controls the expression of the POU-domain transcription factor Acj6 in approximately half of the cells and, in at least one glomerulus, ems function in dendritic targeting is mediated through Acj6. The finding that Drosophila ems, like its murine homologs Emx1/2, is required for the formation of olfactory circuitry implies that conserved genetic programs control olfactory system development in insects and mammals.

  16. Arm-Gal4 inheritance influences development and lifespan in Drosophila melanogaster.

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    Slade, F A; Staveley, B E

    2015-10-19

    The UAS-Gal4 ectopic expression system is a widely used and highly valued tool that allows specific gene expression in Drosophila melanogaster. Yeast transcription factor Gal4 can be directed using D. melanogaster transcriptional control elements, and is often assumed to have little effect on the organism. By evaluation of the consequences of maternal and paternal inheritance of a Gal4 transgene under the transcriptional regulation of armadillo control elements (arm-Gal4), we demonstrated that Gal4 expression could be detrimental to development and longevity. Male progeny expressing arm-Gal4 in the presence of UAS-lacZ transgene had reduced numbers and size of ommatidia, compared to flies expressing UAS-lacZ transgene under the control of other Gal4 transgenes. Aged at 25°C, the median life span of male flies with maternally inherited elav-Gal4 was 70 days, without a responding transgene or with UAS-lacZ. The median life span of maternally inherited arm-Gal4 male flies without a responding transgene was 48 days, and 40 days with the UAS-lacZ transgene. A partial rescue of this phenotype was observed with the expression of UAS-lacZ under paternal arm-Gal4 control, having an average median lifespan of 60 days. This data suggests that arm-Gal4 has detrimental effects on Drosophila development and lifespan that are directly dependent upon parental inheritance, and that the benign responder and reporter gene UAS-lacZ may influence D. melanogaster development. These findings should be taken into consideration during the design and execution of UAS-Gal4 expression experiments.

  17. Role of sensory experience in functional development of Drosophila motor circuits.

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    Fushiki, Akira; Kohsaka, Hiroshi; Nose, Akinao

    2013-01-01

    Neuronal circuits are formed according to a genetically predetermined program and then reconstructed in an experience-dependent manner. While the existence of experience-dependent plasticity has been demonstrated for the visual and other sensory systems, it remains unknown whether this is also the case for motor systems. Here we examined the effects of eliminating sensory inputs on the development of peristaltic movements in Drosophila embryos and larvae. The peristalsis is initially slow and uncoordinated, but gradually develops into a mature pattern during late embryonic stages. We tested whether inhibiting the transmission of specific sensory neurons during this period would have lasting effects on the properties of the sensorimotor circuits. We applied Shibire-mediated inhibition for six hours during embryonic development (15-21 h after egg laying [AEL]) and studied its effects on peristalsis in the mature second- and third-instar larvae. We found that inhibition of chordotonal organs, but not multidendritic neurons, led to a lasting decrease in the speed of larval locomotion. To narrow down the sensitive period, we applied shorter inhibition at various embryonic and larval stages and found that two-hour inhibition during 16-20 h AEL, but not at earlier or later stages, was sufficient to cause the effect. These results suggest that neural activity mediated by specific sensory neurons is involved in the maturation of sensorimotor circuits in Drosophila and that there is a critical period for this plastic change. Consistent with a role of chordotonal neurons in sensory feedback, these neurons were activated during larval peristalsis and acute inhibition of their activity decreased the speed of larval locomotion.

  18. Role of sensory experience in functional development of Drosophila motor circuits.

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    Akira Fushiki

    Full Text Available Neuronal circuits are formed according to a genetically predetermined program and then reconstructed in an experience-dependent manner. While the existence of experience-dependent plasticity has been demonstrated for the visual and other sensory systems, it remains unknown whether this is also the case for motor systems. Here we examined the effects of eliminating sensory inputs on the development of peristaltic movements in Drosophila embryos and larvae. The peristalsis is initially slow and uncoordinated, but gradually develops into a mature pattern during late embryonic stages. We tested whether inhibiting the transmission of specific sensory neurons during this period would have lasting effects on the properties of the sensorimotor circuits. We applied Shibire-mediated inhibition for six hours during embryonic development (15-21 h after egg laying [AEL] and studied its effects on peristalsis in the mature second- and third-instar larvae. We found that inhibition of chordotonal organs, but not multidendritic neurons, led to a lasting decrease in the speed of larval locomotion. To narrow down the sensitive period, we applied shorter inhibition at various embryonic and larval stages and found that two-hour inhibition during 16-20 h AEL, but not at earlier or later stages, was sufficient to cause the effect. These results suggest that neural activity mediated by specific sensory neurons is involved in the maturation of sensorimotor circuits in Drosophila and that there is a critical period for this plastic change. Consistent with a role of chordotonal neurons in sensory feedback, these neurons were activated during larval peristalsis and acute inhibition of their activity decreased the speed of larval locomotion.

  19. The Drosophila histone demethylase dKDM5/LID regulates hematopoietic development.

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    Morán, Tomás; Bernués, Jordi; Azorín, Fernando

    2015-09-15

    dKDM5/LID regulates transcription of essential developmental genes and, thus, is required for different developmental processes. Here, we report the essential contribution of dKDM5/LID to hematopoiesis in Drosophila. Our results show that dKDM5/LID is abundant in hemocytes and that its depletion induces over-proliferation and differentiation defects of larval hemocytes and disrupts organization of the actin cytoskeleton. We also show that dKDM5/LID regulates expression of key factors of hematopoietic development. In particular, dKDM5/LID depletion up-regulates expression of several transcription factors involved in hemocytes proliferation and differentiation as well as of several small-GTPases that link signaling effectors to actin cytoskeleton formation and dynamics.

  20. A cellular memory module conveys epigenetic inheritance of hedgehog expression during Drosophila wing imaginal disc development.

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    Maurange, Cédric; Paro, Renato

    2002-10-15

    In Drosophila, the Trithorax-group (trxG) and Polycomb-group (PcG) proteins interact with chromosomal elements, termed Cellular Memory Modules (CMMs). By modifying chromatin, this ensures a stable heritable maintenance of the transcriptional state of developmental regulators, like the homeotic genes, that is defined embryonically. We asked whether such CMMs could also control expression of genes involved in patterning imaginal discs during larval development. Our results demonstrate that expression of the hedgehog gene, once activated, is maintained by a CMM. In addition, our experiments indicate that the switching of such CMMs to an active state during larval stages, in contrast to embryonic stages, may require specific trans-activators. Our results suggest that the patterning of cells in particular developmental fields in the imaginal discs does not only rely on external cues from morphogens, but also depends on the previous history of the cells, as the control by CMMs ensures a preformatted gene expression pattern.

  1. How complexity increases in development: An analysis of the spatial-temporal dynamics of 1218 genes in Drosophila melanogaster.

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    Salvador-Martínez, Irepan; Salazar-Ciudad, Isaac

    2015-09-15

    One of the most apparent phenomena in development is that it starts with something apparently simple and leads to something clearly complex with a specific and functional structure. At the level of gene expression it seems also clear that the embryo becomes progressively compartmentalized over time and space. However, there have not been any systematic attempts to quantify how this occurs. Here, we present a quantitative analysis of the compartmentalization and spatial complexity of gene expression in Drosophila melanogaster over developmental time by analyzing thousands of gene expression spatial patterns from FlyExpress database. We use three different mathematical measures of compartmentalization of gene expression in space. All these measures show a similar non-linear increase in compartmentalization over time, with the most dramatic change occurring from the maternal to the early gastrula stage. Transcription factors and growth factors showed an earlier compartmentalization. Finally, we partitioned the embryo space in 257 equally sized regions and clustered them depending on their expression similarity, within and between stages. This provides a global overview about the effective degree of differentiation and compartmentalization between body parts at each developmental stage and when and where in the embryo there are more changes, due to signaling or movement.

  2. Rb deficiency during Drosophila eye development deregulates EMC, causing defects in the development of photoreceptors and cone cells.

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    Popova, Milena K; He, Wei; Korenjak, Michael; Dyson, Nicholas J; Moon, Nam-Sung

    2011-12-15

    Retinoblastoma tumor suppressor protein (pRb) regulates various biological processes during development and tumorigenesis. Although the molecular mechanism by which pRb controls cell cycle progression is well characterized, how pRb promotes cell-type specification and differentiation is less understood. Here, we report that Extra Macrochaetae (EMC), the Drosophila homolog of inhibitor of DNA binding/differentiation (ID), is an important protein contributing to the developmental defects caused by Rb deficiency. An emc allele was identified from a genetic screen designed to identify factors that, when overexpressed, cooperate with mutations in rbf1, which encodes one of the two Rb proteins found in Drosophila. EMC overexpression in an rbf1 hypomorphic mutant background induces cone cell and photoreceptor defects but has negligible effects in the wild-type background. Interestingly, a substantial fraction of the rbf1-null ommatidia normally exhibit similar cone cell and photoreceptor defects in the absence of ectopic EMC expression. Detailed EMC expression analyses revealed that RBF1 suppresses expression of both endogenous and ectopic EMC protein in photoreceptors, thus explaining the synergistic effect between EMC overexpression and rbf1 mutations, and the developmental defect observed in rbf1-null ommatidia. Our findings demonstrate that ID family proteins are an evolutionarily conserved determinant of Rb-deficient cells, and play an important role during development.

  3. The insulin receptor is required for the development of the Drosophila peripheral nervous system.

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    Annie Dutriaux

    Full Text Available The Insulin Receptor (InR in Drosophila presents features conserved in its mammalian counterparts. InR is required for growth; it is expressed in the central and embryonic nervous system and modulates the time of differentiation of the eye photoreceptor without altering cell fate. We show that the InR is required for the formation of the peripheral nervous system during larval development and more particularly for the formation of sensory organ precursors (SOPs on the fly notum and scutellum. SOPs arise in the proneural cluster that expresses high levels of the proneural proteins Achaete (Ac and Scute (Sc. The other cells will become epidermis due to lateral inhibition induced by the Notch (N receptor signal that prevents its neighbors from adopting a neural fate. In addition, misexpression of the InR or of other components of the pathway (PTEN, Akt, FOXO induces the development of an abnormal number of macrochaetes that are Drosophila mechanoreceptors. Our data suggest that InR regulates the neural genes ac, sc and sens. The FOXO transcription factor which is localized in the cytoplasm upon insulin uptake, displays strong genetic interaction with the InR and is involved in Ac regulation. The genetic interactions between the epidermal growth factor receptor (EGFR, Ras and InR/FOXO suggest that these proteins cooperate to induce neural gene expression. Moreover, InR/FOXO is probably involved in the lateral inhibition process, since genetic interactions with N are highly significant. These results show that the InR can alter cell fate, independently of its function in cell growth and proliferation.

  4. On the role of the MAGUK proteins encoded by Drosophila varicose during embryonic and postembryonic development

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    Grawe Ferdi

    2008-05-01

    Full Text Available Abstract Background Membrane-associated guanylate kinases (MAGUKs form a family of scaffolding proteins, which are often associated with cellular junctions, such as the vertebrate tight junction, the Drosophila septate junction or the neuromuscular junction. Their capacity to serve as platforms for organising larger protein assemblies results from the presence of several protein-protein interaction domains. They often appear in different variants suggesting that they also mediate dynamic changes in the composition of the complexes. Results Here we show by electron microscopic analysis that Drosophila embryos lacking varicose function fail to develop septate junctions in the tracheae and the epidermis. In the embryo and in imaginal discs varicose expresses two protein isoforms, which belong to the MAGUK family. The two isoforms can be distinguished by the presence or absence of two L27 domains and are differentially affected in different varicose alleles. While the short isoform is essential for viability, the long isoform seems to have a supportive function. Varicose proteins co-localise with Neurexin IV in pleated septate junctions and are necessary, but not sufficient for its recruitment. The two proteins interact in vitro by the PDZ domain of Varicose and the four C-terminal amino acids of Neurexin IV. Postembryonic reduction of varicose function by expressing double-stranded RNA affects pattern formation and morphogenesis of the wing and the development of normal-shaped and -sized eyes. Conclusion Expression of two Varicose isoforms in embryonic epithelia and imaginal discs suggests that the composition of Varicose-mediated protein scaffolds at septate junctions is dynamic, which may have important implications for the modulation of their function.

  5. Spatial reorganization of the endoplasmic reticulum during mitosis relies on mitotic kinase cyclin A in the early Drosophila embryo.

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    Bergman, Zane J; Mclaurin, Justin D; Eritano, Anthony S; Johnson, Brittany M; Sims, Amanda Q; Riggs, Blake

    2015-01-01

    Mitotic cyclin-dependent kinase with their cyclin partners (cyclin:Cdks) are the master regulators of cell cycle progression responsible for regulating a host of activities during mitosis. Nuclear mitotic events, including chromosome condensation and segregation have been directly linked to Cdk activity. However, the regulation and timing of cytoplasmic mitotic events by cyclin:Cdks is poorly understood. In order to examine these mitotic cytoplasmic events, we looked at the dramatic changes in the endoplasmic reticulum (ER) during mitosis in the early Drosophila embryo. The dynamic changes of the ER can be arrested in an interphase state by inhibition of either DNA or protein synthesis. Here we show that this block can be alleviated by micro-injection of Cyclin A (CycA) in which defined mitotic ER clusters gathered at the spindle poles. Conversely, micro-injection of Cyclin B (CycB) did not affect spatial reorganization of the ER, suggesting CycA possesses the ability to initiate mitotic ER events in the cytoplasm. Additionally, RNAi-mediated simultaneous inhibition of all 3 mitotic cyclins (A, B and B3) blocked spatial reorganization of the ER. Our results suggest that mitotic ER reorganization events rely on CycA and that control and timing of nuclear and cytoplasmic events during mitosis may be defined by release of CycA from the nucleus as a consequence of breakdown of the nuclear envelope.

  6. Spatial Reorganization of the Endoplasmic Reticulum during Mitosis Relies on Mitotic Kinase Cyclin A in the Early Drosophila Embryo

    Science.gov (United States)

    Bergman, Zane J.; Mclaurin, Justin D.; Eritano, Anthony S.; Johnson, Brittany M.; Sims, Amanda Q.; Riggs, Blake

    2015-01-01

    Mitotic cyclin-dependent kinase with their cyclin partners (cyclin:Cdks) are the master regulators of cell cycle progression responsible for regulating a host of activities during mitosis. Nuclear mitotic events, including chromosome condensation and segregation have been directly linked to Cdk activity. However, the regulation and timing of cytoplasmic mitotic events by cyclin:Cdks is poorly understood. In order to examine these mitotic cytoplasmic events, we looked at the dramatic changes in the endoplasmic reticulum (ER) during mitosis in the early Drosophila embryo. The dynamic changes of the ER can be arrested in an interphase state by inhibition of either DNA or protein synthesis. Here we show that this block can be alleviated by micro-injection of Cyclin A (CycA) in which defined mitotic ER clusters gathered at the spindle poles. Conversely, micro-injection of Cyclin B (CycB) did not affect spatial reorganization of the ER, suggesting CycA possesses the ability to initiate mitotic ER events in the cytoplasm. Additionally, RNAi-mediated simultaneous inhibition of all 3 mitotic cyclins (A, B and B3) blocked spatial reorganization of the ER. Our results suggest that mitotic ER reorganization events rely on CycA and that control and timing of nuclear and cytoplasmic events during mitosis may be defined by release of CycA from the nucleus as a consequence of breakdown of the nuclear envelope. PMID:25689737

  7. [Apropos of the studies of Lewis, Nusslein-Volhard and Wieschaus, 1995 Nobel prize winners, on the genetic mechanisms of embryonic development of drosophila. A model for human cancer progression].

    Science.gov (United States)

    Cillo, C

    1996-07-01

    EB Lewis, C Nusslein-Volhard and E Wieschaus were the winners of the Nobel prize in 1995 for the discovery of genes controling the embryonic development in drosophila. Drosophila development is dependent on sequential activities of three types of genes: the maternal genes, the segmentation genes, and the homeotic genes which are responsible for the segment identity and finally for the building of the body. Mutations of these genes are spectacular because they affect the body structure formed from individual segments. Therefore, the molecular processes regulating the development of inferior organisms such as yeast or more complex as the vertebrates were elucidated by these three researchers. These early biological mechanisms regulate the cell life through interactions with neighbouring cells. We speculate that any alteration of these processes might be implicated in cancer. Understanding of these molecular mechanisms which control cell interactions in cancer constitutes a basis for definition of new prognostic markers and putatively novel therapeutic approaches.

  8. Understanding Early Sexual Development (For Parents)

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    ... Reading Is Your Child Too Busy? Helping Your Child Adjust to Preschool School Lunches Kids and Food: 10 Tips for Parents Healthy Habits for TV, Video Games, and the Internet Understanding Early Sexual Development KidsHealth > For Parents > Understanding Early Sexual Development Print ...

  9. Ctr9, a Key Component of the Paf1 Complex, Affects Proliferation and Terminal Differentiation in the Developing Drosophila Nervous System

    Science.gov (United States)

    Bahrampour, Shahrzad; Thor, Stefan

    2016-01-01

    The Paf1 protein complex (Paf1C) is increasingly recognized as a highly conserved and broadly utilized regulator of a variety of transcriptional processes. These include the promotion of H3K4 and H3K36 trimethylation, H2BK123 ubiquitination, RNA Pol II transcriptional termination, and also RNA-mediated gene silencing. Paf1C contains five canonical protein components, including Paf1 and Ctr9, which are critical for overall complex integrity, as well as Rtf1, Leo1, and Cdc73/Parafibromin(Hrpt2)/Hyrax. In spite of a growing appreciation for the importance of Paf1C from yeast and mammalian studies, there has only been limited work in Drosophila. Here, we provide the first detailed phenotypic study of Ctr9 function in Drosophila. We found that Ctr9 mutants die at late embryogenesis or early larval life, but can be partly rescued by nervous system reexpression of Ctr9. We observed a number of phenotypes in Ctr9 mutants, including increased neuroblast numbers, increased nervous system proliferation, as well as downregulation of many neuropeptide genes. Analysis of cell cycle and regulatory gene expression revealed upregulation of the E2f1 cell cycle factor, as well as changes in Antennapedia and Grainy head expression. We also found reduction of H3K4me3 modification in the embryonic nervous system. Genome-wide transcriptome analysis points to additional downstream genes that may underlie these Ctr9 phenotypes, revealing gene expression changes in Notch pathway target genes, cell cycle genes, and neuropeptide genes. In addition, we find significant effects on the gene expression of metabolic genes. These findings reveal that Ctr9 is an essential gene that is necessary at multiple stages of nervous system development, and provides a starting point for future studies of the Paf1C in Drosophila. PMID:27520958

  10. Mef2 interacts with the Notch pathway during adult muscle development in Drosophila melanogaster.

    Science.gov (United States)

    Caine, Charlotte; Kasherov, Petar; Silber, Joël; Lalouette, Alexis

    2014-01-01

    Myogenesis of indirect flight muscles (IFMs) in Drosophila melanogaster follows a well-defined cellular developmental scheme. During embryogenesis, a set of cells, the Adult Muscle Precursors (AMPs), are specified. These cells will become proliferating myoblasts during the larval stages which will then give rise to the adult IFMs. Although the cellular aspect of this developmental process is well studied, the molecular biology behind the different stages is still under investigation. In particular, the interactions required during the transition from proliferating myoblasts to differentiated myoblasts ready to fuse to the muscle fiber. It has been previously shown that the Notch pathway is active in proliferating myoblasts, and that this pathway is inhibited in developing muscle fibers. Furthermore, the Myocyte Enhancing Factor 2 (Mef2), Vestigial (Vg) and Scalloped (Sd) transcription factors are necessary for IFM development and that Vg is required for Notch pathway repression in differentiating fibers. Here we examine the interactions between Notch and Mef2 and mechanisms by which the Notch pathway is inhibited during differentiation. We show that Mef2 is capable of inhibiting the Notch pathway in non myogenic cells. A previous screen for Mef2 potential targets identified Delta a component of the Notch pathway. Dl is expressed in Mef2 and Sd-positive developing fibers. Our results show that Mef2 and possibly Sd regulate a Dl enhancer specifically expressed in the developing IFMs and that Mef2 is required for Dl expression in developing IFMs.

  11. La conducta de larvas de Drosophila (Diptera; Drosophilidae: su etología, desarrollo, genética y evolución The behavior of Drosophila larvae: their ethology, development, genetics and evolution

    Directory of Open Access Journals (Sweden)

    RAÚL GODOY-HERRERA

    2001-03-01

    Full Text Available Este trabajo, en honor al Profesor Doctor Danko Brncic Juricic (Q.E.P.D., es una revisión de nuestras contribuciones sobre la etología, desarrollo, genética y evolución de patrones de conducta de larvas de Drosophila. Se discute el desarrollo de conductas larvales de forrajeo y sus bases hereditarias. También se discuten estrategias de investigación dirigidas a entender las relaciones entre genotipo y conducta durante el desarrollo de los organismos. Se relacionan patrones de desarrollo de conductas larvales con la filogenia de las especies del grupo mesophragmatica de Drosophila. Finalmente, se distingue entre evolución de elementos de conducta simple y evolución de conductas complejasThis is a review about our contributions in ethology, development, genetics, and evolution of larval behavioral patterns of Drosophila in honor of the late Professor Doctor Danko Brncic Juricic. The developmental behavioral genetics of larval foraging and pupation of Drosophila are discussed. It is also emphasized the importance of research strategies lead to understand properly the relationships between genotype and behavior during development of the organisms. Finally, a comparison between phylogenetic relationships of six Drosophila species of the mesophragmatica group and their developmental patterns of larval behaviors is provided

  12. From Embryo to Adult: piRNA-Mediated Silencing throughout Germline Development in Drosophila

    Science.gov (United States)

    Marie, Pauline P.; Ronsseray, Stéphane; Boivin, Antoine

    2016-01-01

    In metazoan germ cells, transposable element activity is repressed by small noncoding PIWI-associated RNAs (piRNAs). Numerous studies in Drosophila have elucidated the mechanism of this repression in the adult germline. However, when and how transposable element repression is established during germline development has not been addressed. Here, we show that homology-dependent trans silencing is active in female primordial germ cells from late embryogenesis through pupal stages, and that genes related to the adult piRNA pathway are required for silencing during development. In larval gonads, we detect rhino-dependent piRNAs indicating de novo biogenesis of functional piRNAs during development. Those piRNAs exhibit the molecular signature of the “ping-pong” amplification step. Moreover, we show that Heterochromatin Protein 1a is required for the production of piRNAs coming from telomeric transposable elements. Furthermore, as in adult ovaries, incomplete, bimodal, and stochastic repression resembling variegation can occur at all developmental stages. Clonal analysis indicates that the repression status established in embryonic germ cells is maintained until the adult stage, suggesting the implication of a cellular memory mechanism. Taken together, data presented here show that piRNAs and their associated proteins are epigenetic components of a continuous repression system throughout germ cell development. PMID:27932388

  13. From Embryo to Adult: piRNA-Mediated Silencing throughout Germline Development in Drosophila

    Directory of Open Access Journals (Sweden)

    Pauline P. Marie

    2017-02-01

    Full Text Available In metazoan germ cells, transposable element activity is repressed by small noncoding PIWI-associated RNAs (piRNAs. Numerous studies in Drosophila have elucidated the mechanism of this repression in the adult germline. However, when and how transposable element repression is established during germline development has not been addressed. Here, we show that homology-dependent trans silencing is active in female primordial germ cells from late embryogenesis through pupal stages, and that genes related to the adult piRNA pathway are required for silencing during development. In larval gonads, we detect rhino-dependent piRNAs indicating de novo biogenesis of functional piRNAs during development. Those piRNAs exhibit the molecular signature of the “ping-pong” amplification step. Moreover, we show that Heterochromatin Protein 1a is required for the production of piRNAs coming from telomeric transposable elements. Furthermore, as in adult ovaries, incomplete, bimodal, and stochastic repression resembling variegation can occur at all developmental stages. Clonal analysis indicates that the repression status established in embryonic germ cells is maintained until the adult stage, suggesting the implication of a cellular memory mechanism. Taken together, data presented here show that piRNAs and their associated proteins are epigenetic components of a continuous repression system throughout germ cell development.

  14. The Drosophila DOCK family protein Sponge is required for development of the air sac primordium.

    Science.gov (United States)

    Morishita, Kazushge; Anh Suong, Dang Ngoc; Yoshida, Hideki; Yamaguchi, Masamitsu

    2017-05-15

    Dedicator of cytokinesis (DOCK) family genes are known as DOCK1-DOCK11 in mammals. DOCK family proteins mainly regulate actin filament polymerization and/or depolymerization and are GEF proteins, which contribute to cellular signaling events by activating small G proteins. Sponge (Spg) is a Drosophila counterpart to mammalian DOCK3/DOCK4, and plays a role in embryonic central nervous system development, R7 photoreceptor cell differentiation, and adult thorax development. In order to conduct further functional analyses on Spg in vivo, we examined its localization in third instar larval wing imaginal discs. Immunostaining with purified anti-Spg IgG revealed that Spg mainly localized in the air sac primordium (ASP) in wing imaginal discs. Spg is therefore predicted to play an important role in the ASP. The specific knockdown of Spg by the breathless-GAL4 driver in tracheal cells induced lethality accompanied with a defect in ASP development and the induction of apoptosis. The monitoring of ERK signaling activity in wing imaginal discs by immunostaining with anti-diphospho-ERK IgG revealed reductions in the ERK signal cascade in Spg knockdown clones. Furthermore, the overexpression of D-raf suppressed defects in survival and the proliferation of cells in the ASP induced by the knockdown of Spg. Collectively, these results indicate that Spg plays a critical role in ASP development and tracheal cell viability that is mediated by the ERK signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Early adversity, neural development, and inflammation.

    Science.gov (United States)

    Chiang, Jessica J; Taylor, Shelley E; Bower, Julienne E

    2015-12-01

    Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.

  16. Identification and characterization of autosomal genes that interact with glass in the developing Drosophila eye

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Chaoyong; Liu, Hui; Zhou, Ying; Moses, K. [Univ. of Southern California, Los Angeles, CA (United States)

    1996-04-01

    The glass gene encodes a zinc finger, DNA-binding protein that is required for photoreceptor cell development in Drosophila melanogaster. In the developing compound eye, glass function is regulated at two points: (1) the protein is expressed in all cells` nuclei posterior to the morphogenetic furrow and (2) the ability of the Glass protein to regulate downstream genes is largely limited to the developing photoreceptor cells. We conducted a series of genetic screen for autosomal dominant second-site modifiers of the weak allele glass, to discover genes with products that may regulate glass function at either of these levels. Seventy-six dominant enhancer mutations were recovered (and no dominant suppressors). Most of these dominant mutations are in essential genes and are associated with recessive lethality. We have assigned these mutations to 23 complementation groups that include multiple alleles of Star and hedgehog as well as single alleles of Delta, roughened eye, glass and hairy. Mutations in 18 of the complementation groups are embryonic lethals, and of these, 13 show abnormal adult retinal phenotypes in homozygous clones, usually with altered numbers of photoreceptor cells in some of the ommatidia. 116 refs., 9 figs., 2 tabs.

  17. Atrazine exposure affects longevity, development time and body size in Drosophila melanogaster.

    Science.gov (United States)

    Marcus, Sarah R; Fiumera, Anthony C

    2016-01-01

    Atrazine is the one of the most widely used herbicides in the United States and non-target organisms may encounter it in the environment. Atrazine is known to affect male reproduction in both vertebrates and invertebrates but less is known about its effects on other fitness traits. Here we assessed the effects of five different chronic exposure levels on a variety of fitness traits in Drosophila melanogaster. We measured male and female longevity, development time, proportion pupated, proportion emerged, body size, female mating rate, fertility and fecundity. Atrazine exposure decreased the proportion pupated, the proportion emerged and adult survival. Development time was also affected by atrazine and exposed flies pupated and emerged earlier than controls. Although development time was accelerated, body size was actually larger in some of the exposures. Atrazine exposure had no effect on female mating rate and the effects on female fertility and fecundity were only observed in one of the two independent experimental blocks. Many of the traits showed non-monotonic dose response curves, where the intermediate concentrations showed the largest effects. Overall this study shows that atrazine influences a variety of life history traits in the model genetic system, D. melanogaster, and future studies should aim to identify the molecular mechanisms of toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Snipper, an Eri1 homologue, affects histone mRNA abundance and is crucial for normal Drosophila melanogaster development.

    Science.gov (United States)

    Alexiadis, Anastasios; Delidakis, Christos; Kalantidis, Kriton

    2017-07-01

    The conserved 3'-5' RNA exonuclease ERI1 is implicated in RNA interference inhibition, 5.8S rRNA maturation and histone mRNA maturation and turnover. The single ERI1 homologue in Drosophila melanogaster Snipper (Snp) is a 3'-5' exonuclease, but its in vivo function remains elusive. Here, we report Snp requirement for normal Drosophila development, since its perturbation leads to larval arrest and tissue-specific downregulation results in abnormal tissue development. Additionally, Snp directly interacts with histone mRNA, and its depletion results in drastic reduction in histone transcript levels. We propose that Snp protects the 3'-ends of histone mRNAs and upon its absence, histone transcripts are readily degraded. This in turn may lead to cell cycle delay or arrest, causing growth arrest and developmental perturbations. © 2017 Federation of European Biochemical Societies.

  19. Rho-kinase regulates tissue morphogenesis via non-muscle myosin and LIM-kinase during Drosophila development

    Directory of Open Access Journals (Sweden)

    Settleman Jeffrey

    2006-08-01

    Full Text Available Abstract Background The Rho-kinases (ROCKs are major effector targets of the activated Rho GTPase that have been implicated in many of the Rho-mediated effects on cell shape and movement via their ability to affect acto-myosin contractility. The role of ROCKs in cell shape change and motility suggests a potentially important role for Rho-ROCK signaling in tissue morphogenesis during development. Indeed, in Drosophila, a single ROCK ortholog, DRok, has been identified and has been found to be required for establishing planar cell polarity. Results We have examined a potential role for DRok in additional aspects of tissue morphogenesis using an activated form of the protein in transgenic flies. Our findings demonstrate that DRok activity can influence multiple morphogenetic processes, including eye and wing development. Furthermore, genetic studies reveal that Drok interacts with multiple downstream effectors of the Rho GTPase signaling pathway, including non-muscle myosin heavy chain, adducin, and Diaphanous in those developmental processes. Finally, in overexpression studies, we determined that Drok and Drosophila Lim-kinase interact in the developing nervous system. Conclusion These findings indicate widespread diverse roles for DRok in tissue morphogenesis during Drosophila development, in which multiple DRok substrates appear to be required.

  20. The actin regulators Enabled and Diaphanous direct distinct protrusive behaviors in different tissues during Drosophila development.

    Science.gov (United States)

    Nowotarski, Stephanie H; McKeon, Natalie; Moser, Rachel J; Peifer, Mark

    2014-10-15

    Actin-based protrusions are important for signaling and migration during development and homeostasis. Defining how different tissues in vivo craft diverse protrusive behaviors using the same genomic toolkit of actin regulators is a current challenge. The actin elongation factors Diaphanous and Enabled both promote barbed-end actin polymerization and can stimulate filopodia in cultured cells. However, redundancy in mammals and Diaphanous' role in cytokinesis limited analysis of whether and how they regulate protrusions during development. We used two tissues driving Drosophila dorsal closure--migratory leading-edge (LE) and nonmigratory amnioserosal (AS) cells--as models to define how cells shape distinct protrusions during morphogenesis. We found that nonmigratory AS cells produce filopodia that are morphologically and dynamically distinct from those of LE cells. We hypothesized that differing Enabled and/or Diaphanous activity drives these differences. Combining gain- and loss-of-function with quantitative approaches revealed that Diaphanous and Enabled each regulate filopodial behavior in vivo and defined a quantitative "fingerprint"--the protrusive profile--which our data suggest is characteristic of each actin regulator. Our data suggest that LE protrusiveness is primarily Enabled driven, whereas Diaphanous plays the primary role in the AS, and reveal each has roles in dorsal closure, but its robustness ensures timely completion in their absence.

  1. DAAM is required for thin filament formation and Sarcomerogenesis during muscle development in Drosophila.

    Science.gov (United States)

    Molnár, Imre; Migh, Ede; Szikora, Szilárd; Kalmár, Tibor; Végh, Attila G; Deák, Ferenc; Barkó, Szilvia; Bugyi, Beáta; Orfanos, Zacharias; Kovács, János; Juhász, Gábor; Váró, György; Nyitrai, Miklós; Sparrow, John; Mihály, József

    2014-02-01

    During muscle development, myosin and actin containing filaments assemble into the highly organized sarcomeric structure critical for muscle function. Although sarcomerogenesis clearly involves the de novo formation of actin filaments, this process remained poorly understood. Here we show that mouse and Drosophila members of the DAAM formin family are sarcomere-associated actin assembly factors enriched at the Z-disc and M-band. Analysis of dDAAM mutants revealed a pivotal role in myofibrillogenesis of larval somatic muscles, indirect flight muscles and the heart. We found that loss of dDAAM function results in multiple defects in sarcomere development including thin and thick filament disorganization, Z-disc and M-band formation, and a near complete absence of the myofibrillar lattice. Collectively, our data suggest that dDAAM is required for the initial assembly of thin filaments, and subsequently it promotes filament elongation by assembling short actin polymers that anneal to the pointed end of the growing filaments, and by antagonizing the capping protein Tropomodulin.

  2. DAAM is required for thin filament formation and Sarcomerogenesis during muscle development in Drosophila.

    Directory of Open Access Journals (Sweden)

    Imre Molnár

    2014-02-01

    Full Text Available During muscle development, myosin and actin containing filaments assemble into the highly organized sarcomeric structure critical for muscle function. Although sarcomerogenesis clearly involves the de novo formation of actin filaments, this process remained poorly understood. Here we show that mouse and Drosophila members of the DAAM formin family are sarcomere-associated actin assembly factors enriched at the Z-disc and M-band. Analysis of dDAAM mutants revealed a pivotal role in myofibrillogenesis of larval somatic muscles, indirect flight muscles and the heart. We found that loss of dDAAM function results in multiple defects in sarcomere development including thin and thick filament disorganization, Z-disc and M-band formation, and a near complete absence of the myofibrillar lattice. Collectively, our data suggest that dDAAM is required for the initial assembly of thin filaments, and subsequently it promotes filament elongation by assembling short actin polymers that anneal to the pointed end of the growing filaments, and by antagonizing the capping protein Tropomodulin.

  3. Conserved genetic pathways controlling the development of the diffuse endocrine system in vertebrates and Drosophila.

    Science.gov (United States)

    Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina L

    2010-05-01

    The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type.

  4. Pathways involved in Drosophila and human cancer development: the Notch, Hedgehog, Wingless, Runt, and Trithorax pathway.

    Science.gov (United States)

    Geissler, Klaus; Zach, Otto

    2012-05-01

    Animal models are established tools to study basic questions of biology in a systematic way. They have greatly facilitated our understanding of the mechanisms by which nature forms and maintains organisms. Much of the knowledge on molecular changes underlying the development of organisms originates from research in the fruit fly model Drosophila melanogaster. Vertebrate models including the mouse and zebrafish model, but also other animal models coming from different corners of the animal kingdom have shown that much of the basic machinery of development is essentially identical, not just in all vertebrates but in all major phyla of invertebrates too. Moreover, key elements of this machinery have been demonstrated to be involved in recurrent molecular abnormalities detected in tumor-tissue from patients, indicating their implication in the genesis of human cancer. Thus, research in this field has become a common topic for both biologists and hemato-oncologists. In this review, we summarize current knowledge on some of these key elements and molecular pathways such as Notch, Hedgehog, Wingless, Runt, and Trithorax that have been originally described and studied in animal models and which seem to play a major role in the pathophysiology and targeted management of human cancer.

  5. Non-apoptotic function of apoptotic proteins in the development of Malpighian tubules of Drosophila melanogaster

    Indian Academy of Sciences (India)

    Madhu G Tapadia; Naveen K Gautam

    2011-08-01

    Drosophila metamorphosis is characterized by the histolysis of larval structures by programmed cell death, which paves the way for the establishment of adult-specific structures under the influence of the steroid hormone ecdysone. Malpighian tubules function as an excretory system and are one of the larval structures that are not destroyed during metamorphosis and are carried over to adulthood. The pupal Malpighian tubules evade destruction in spite of expressing apoptotic proteins, Reaper, Hid, Grim, Dronc and Drice. Here we show that in the Malpighian tubules expression of apoptotic proteins commences right from embryonic development and continues throughout the larval stages. Overexpression of these proteins in the Malpighian tubules causes larval lethality resulting in malformed tubules. The number and regular organization of principal and stellate cells of Malpighian tubules is disturbed, in turn disrupting the physiological functioning of the tubules as well. Strikingly, the localization of -tubulin, F-actin and Disclarge (Dlg) is also disrupted. These results suggest that the apoptotic proteins could be having non-apoptotic function in the development of Malpighian tubules.

  6. Moral Development Interventions in Early Adolescence.

    Science.gov (United States)

    Enright, Robert D; And Others

    1983-01-01

    Strategies for promoting moral development in early adolescence reviewed include the "plus-one" model, Deliberate Psychological Education, didactic courses in social studies, and a high school Just Community on moral reasoning. (CJ)

  7. Characterization of the split ends-like gene spenito reveals functional antagonism between SPOC family members during Drosophila eye development.

    Science.gov (United States)

    Jemc, Jennifer; Rebay, Ilaria

    2006-05-01

    The novel family of SPOC domain proteins is composed of broadly conserved nuclear factors that fall into two subclasses, termed large and small, based on protein size. Members of the large subgroup, which includes Drosophila SPEN and human SHARP, have been characterized as transcriptional corepressors acting downstream of a variety of essential cell signaling pathways, while those of the small subclass have remained largely unstudied. Since SPEN has been implicated in Drosophila eye development, and the small SPOC protein NITO is also expressed in the developing eye, we have used this context to perform a structure-function analysis of NITO and to examine the relationship between the two SPOC family subclasses. Our results demonstrate that the phenotypes obtained from overexpressing NITO share striking similarity to those associated with loss of spen. Dosage-sensitive genetic interactions further support a model of functional antagonism between NITO and SPEN during Drosophila eye development. These results suggest that large and small SPOC family proteins may have opposing functions in certain developmental contexts.

  8. Early development of visual recognition.

    Science.gov (United States)

    Plebe, Alessio; Domenella, Rosaria Grazia

    2006-01-01

    The most important ability of the human vision is object recognition, yet it is exactly the less understood aspect of the vision system. Computational models have been helpful in progressing towards an explanation of this obscure cognitive ability, and today it is possible to conceive more refined models, thanks to the new availability of neuroscientific data about the human visual cortex. This work proposes a model of the development of the object recognition capability, under a different perspective with respect to the most common approaches, with a precise theoretical epistemology. It is assumed that the main processing functions involved in recognition are not genetically determined and hardwired in the neural circuits, but are the result of interactions between epigenetic influences and the basic neural plasticity mechanisms. The model is organized in modules related with the main visual biological areas, and is implemented mainly using the LISSOM architecture, a recent self-organizing algorithm closely reflecting the essential behavior of cortical circuits.

  9. CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos

    Directory of Open Access Journals (Sweden)

    Ng Fanny

    2008-12-01

    Full Text Available Abstract Background The Drosophila circadian oscillator is composed of transcriptional feedback loops in which CLOCK-CYCLE (CLK-CYC heterodimers activate their feedback regulators period (per and timeless (tim via E-box mediated transcription. These feedback loop oscillators are present in distinct clusters of dorsal and lateral neurons in the adult brain, but how this pattern of expression is established during development is not known. Since CLK is required to initiate feedback loop function, defining the pattern of CLK expression in embryos and larvae will shed light on oscillator neuron development. Results A novel CLK antiserum is used to show that CLK expression in the larval CNS and adult brain is limited to circadian oscillator cells. CLK is initially expressed in presumptive small ventral lateral neurons (s-LNvs, dorsal neurons 2 s (DN2s, and dorsal neuron 1 s (DN1s at embryonic stage (ES 16, and this CLK expression pattern persists through larval development. PER then accumulates in all CLK-expressing cells except presumptive DN2s during late ES 16 and ES 17, consistent with the delayed accumulation of PER in adult oscillator neurons and antiphase cycling of PER in larval DN2s. PER is also expressed in non-CLK-expressing cells in the embryonic CNS starting at ES 12. Although PER expression in CLK-negative cells continues in ClkJrk embryos, PER expression in cells that co-express PER and CLK is eliminated. Conclusion These data demonstrate that brain oscillator neurons begin development during embryogenesis, that PER expression in non-oscillator cells is CLK-independent, and that oscillator phase is an intrinsic characteristic of brain oscillator neurons. These results define the temporal and spatial coordinates of factors that initiate Clk expression, imply that circadian photoreceptors are not activated until the end of embryogenesis, and suggest that PER functions in a different capacity before oscillator cell development is

  10. Arginine methylation of SmB is required for Drosophila germ cell development.

    Science.gov (United States)

    Anne, Joël

    2010-09-01

    Sm proteins constitute the common core of spliceosomal small nuclear ribonucleoproteins. Although Sm proteins are known to be methylated at specific arginine residues within the C-terminal arginine-glycine dipeptide (RG) repeats, the biological relevance of these modifications remains unknown. In this study, a tissue-specific function of arginine methylation of the SmB protein was identified in Drosophila. Analysis of the distribution of SmB during oogenesis revealed that this protein accumulates at the posterior pole of the oocyte, a cytoplasmic region containing the polar granules, which are necessary for the formation of primordial germ cells. The pole plasm localisation of SmB requires the methylation of arginine residues in its RG repeats by the Capsuléen-Valois methylosome complex. Functional studies showed that the methylation of these arginine residues is essential for distinct processes of the germline life cycle, including germ cell formation, migration and differentiation. In particular, the methylation of a subset of these arginine residues appears essential for the anchoring of the polar granules at the posterior cortex of the oocyte, whereas the methylation of another subset controls germ cell migration during embryogenesis. These results demonstrate a crucial role of arginine methylation in directing the subcellular localisation of SmB and that this modification contributes specifically to the establishment and development of germ cells.

  11. Cofilin-mediated actin dynamics promotes actin bundle formation during Drosophila bristle development.

    Science.gov (United States)

    Wu, Jing; Wang, Heng; Guo, Xuan; Chen, Jiong

    2016-08-15

    The actin bundle is an array of linear actin filaments cross-linked by actin-bundling proteins, but its assembly and dynamics are not as well understood as those of the branched actin network. Here we used the Drosophila bristle as a model system to study actin bundle formation. We found that cofilin, a major actin disassembly factor of the branched actin network, promotes the formation and positioning of actin bundles in the developing bristles. Loss of function of cofilin or AIP1, a cofactor of cofilin, each resulted in increased F-actin levels and severe defects in actin bundle organization, with the defects from cofilin deficiency being more severe. Further analyses revealed that cofilin likely regulates actin bundle formation and positioning by the following means. First, cofilin promotes a large G-actin pool both locally and globally, likely ensuring rapid actin polymerization for bundle initiation and growth. Second, cofilin limits the size of a nonbundled actin-myosin network to regulate the positioning of actin bundles. Third, cofilin prevents incorrect assembly of branched and myosin-associated actin filament into bundles. Together these results demonstrate that the interaction between the dynamic dendritic actin network and the assembling actin bundles is critical for actin bundle formation and needs to be closely regulated.

  12. crumbs and stardust, two genes of Drosophila required for the development of epithelial cell polarity.

    Science.gov (United States)

    Knust, E; Tepass, U; Wodarz, A

    1993-01-01

    Loss-of-function mutations in the Drosophila genes crumbs and stardust are embryonic lethal and cause a breakdown of ectodermally derived epithelia during organogenesis, leading to formation of irregular cell clusters and extensive cell death in some epithelia. The mutant phenotype develops gradually and affects the various epithelia to different extents. crumbs encodes a large transmembrane protein with 30 EGF-like repeats and four laminin A G-domain-like repeats in its extracellular domain, suggesting its participation in protein-protein interactions. The CRUMBS protein is exclusively expressed on the apical membrane of all ectodermally derived epithelia, the tissues affected in crumbs and stardust mutant embryos. The gene function is completely abolished by a crumbs mutation that causes production of a protein with a truncated cytoplasmic domain. Instead of being apically localized as in wild-type, the mutant CRUMBS protein is diffusely distributed in the cytoplasm; this occurs before any morphologically detectable cellular phenotype is visible, suggesting that targeting of proteins is affected in crumbs mutant embryos. Later, the protein can be detected on the apical and basolateral membranes. Mutations in stardust produce a phenotype nearly identical to that associated with crumbs mutations, suggesting that both genes are functionally related. Double mutant combinations and gene dosage studies suggest that both genes are part of a common genetic pathway, in which stardust acts downstream of crumbs.

  13. Identification of Mushroom body miniature, a zinc-finger protein implicated in brain development of Drosophila

    Science.gov (United States)

    Raabe, Thomas; Clemens-Richter, Susanne; Twardzik, Thomas; Ebert, Anselm; Gramlich, Gertrud; Heisenberg, Martin

    2004-01-01

    The mushroom bodies are bilaterally arranged structures in the protocerebrum of Drosophila and most other insect species. Mutants with altered mushroom body structure have been instrumental not only in establishing their role in distinct behavioral functions but also in identifying the molecular pathways that control mushroom body development. The mushroom body miniature1 (mbm1) mutation results in grossly reduced mushroom bodies and odor learning deficits in females. With a survey of genomic rescue constructs, we have pinpointed mbm1 to a single transcription unit and identified a single nucleotide exchange in the 5′ untranslated region of the corresponding transcript resulting in a reduced expression of the protein. The most obvious feature of the Mbm protein is a pair of C2HC zinc fingers, implicating a function of the protein in binding nucleic acids. Immunohistochemical analysis shows that expression of the Mbm protein is not restricted to the mushroom bodies. BrdUrd labeling experiments indicate a function of Mbm in neuronal precursor cell proliferation. PMID:15375215

  14. Roles of the troponin isoforms during indirect flight muscle development in Drosophila

    Indian Academy of Sciences (India)

    Salam Herojeet Singh; Prabodh Kumar; Nallur B. Ramachandra; Upendra Nongthomba

    2014-08-01

    Troponin proteins in cooperative interaction with tropomyosin are responsible for controlling the contraction of the striated muscles in response to changes in the intracellular calcium concentration. Contractility of the muscle is determined by the constituent protein isoforms, and the isoforms can switch over from one form to another depending on physiological demands and pathological conditions. In Drosophila, amajority of themyofibrillar proteins in the indirect flight muscles (IFMs) undergo post-transcriptional and post-translational isoform changes during pupal to adult metamorphosis to meet the high energy and mechanical demands of flight. Using a newly generated Gal4 strain (UH3-Gal4) which is expressed exclusively in the IFMs, during later stages of development, we have looked at the developmental and functional importance of each of the troponin subunits (troponin-I, troponin-T and troponin-C) and their isoforms. We show that all the troponin subunits are required for normal myofibril assembly and flight, except for the troponin-C isoform 1 (TnC1). Moreover, rescue experiments conducted with troponin-I embryonic isoform in the IFMs, where flies were rendered flightless, show developmental and functional differences of TnI isoforms and importance of maintaining the right isoform.

  15. Roles of the troponin isoforms during indirect flight muscle development in Drosophila.

    Science.gov (United States)

    Singh, Salam Herojeet; Kumar, Prabodh; Ramachandra, Nallur B; Nongthomba, Upendra

    2014-08-01

    Troponin proteins in cooperative interaction with tropomyosin are responsible for controlling the contraction of the striated muscles in response to changes in the intracellular calcium concentration. Contractility of the muscle is determined by the constituent protein isoforms, and the isoforms can switch over from one form to another depending on physiological demands and pathological conditions. In Drosophila, amajority of themyofibrillar proteins in the indirect flight muscles (IFMs) undergo post-transcriptional and post-translational isoform changes during pupal to adult metamorphosis to meet the high energy and mechanical demands of flight. Using a newly generated Gal4 strain (UH3-Gal4) which is expressed exclusively in the IFMs, during later stages of development, we have looked at the developmental and functional importance of each of the troponin subunits (troponin-I, troponin-T and troponin-C) and their isoforms. We show that all the troponin subunits are required for normal myofibril assembly and flight, except for the troponin-C isoform 1 (TnC1). Moreover, rescue experiments conducted with troponin-I embryonic isoform in the IFMs, where flies were rendered flightless, show developmental and functional differences of TnI isoforms and importance of maintaining the right isoform.

  16. Regulation of wingless signaling by the CKI family in Drosophila limb development.

    Science.gov (United States)

    Zhang, Lei; Jia, Jianhang; Wang, Bing; Amanai, Kazuhito; Wharton, Keith A; Jiang, Jin

    2006-11-01

    The Wingless (Wg)/Wnt signaling pathway regulates a myriad of developmental processes and its malfunction leads to human disorders including cancer. Recent studies suggest that casein kinase I (CKI) family members play pivotal roles in the Wg/Wnt pathway. However, genetic evidence for the involvement of CKI family members in physiological Wg/Wnt signaling events is lacking. In addition, there are conflicting reports regarding whether a given CKI family member functions as a positive or negative regulator of the pathway. Here we examine the roles of seven CKI family members in Wg signaling during Drosophila limb development. We find that increased CKIepsilon stimulates whereas dominant-negative or a null CKIepsilon mutation inhibits Wg signaling. In contrast, inactivation of CKIalpha by RNA interference (RNAi) leads to ectopic Wg signaling. Interestingly, hypomorphic CKIepsilon mutations synergize with CKIalpha RNAi to induce ectopic Wg signaling, revealing a negative role for CKIepsilon. Conversely, CKIalpha RNAi enhances the loss-of-Wg phenotypes caused by CKIepsilon null mutation, suggesting a positive role for CKIalpha. While none of the other five CKI isoforms can substitute for CKIalpha in its inhibitory role in the Wg pathway, several CKI isoforms including CG12147 exhibit a positive role based on overexpression. Moreover, loss of Gilgamesh (Gish)/CKIgamma attenuates Wg signaling activity. Finally, we provide evidence that several CKI isoforms including CKIalpha and Gish/CKIgamma can phosphorylate the Wg coreceptor Arrow (Arr), which may account, at least in part, for their positive roles in the Wg pathway.

  17. Drosophila Crumbs prevents ectopic Notch activation in developing wings by inhibiting ligand-independent endocytosis.

    Science.gov (United States)

    Nemetschke, Linda; Knust, Elisabeth

    2016-12-01

    Many signalling components are apically restricted in epithelial cells, and receptor localisation and abundance is key for morphogenesis and tissue homeostasis. Hence, controlling apicobasal epithelial polarity is crucial for proper signalling. Notch is a ubiquitously expressed, apically localised receptor, which performs a plethora of functions; therefore, its activity has to be tightly regulated. Here, we show that Drosophila Crumbs, an evolutionarily conserved polarity determinant, prevents Notch endocytosis in developing wings through direct interaction between the two proteins. Notch endocytosis in the absence of Crumbs results in the activation of the ligand-independent, Deltex-dependent Notch signalling pathway, and does not require the ligands Delta and Serrate or γ-secretase activity. This function of Crumbs is not due to general defects in apicobasal polarity, as localisation of other apical proteins is unaffected. Our data reveal a mechanism to explain how Crumbs directly controls localisation and trafficking of the potent Notch receptor, and adds yet another aspect of Crumbs regulation in Notch pathway activity. Furthermore, our data highlight a close link between the apical determinant Crumbs, receptor trafficking and tissue homeostasis.

  18. Transcriptional activity and nuclear localization of Cabut, the Drosophila ortholog of vertebrate TGF-β-inducible early-response gene (TIEG proteins.

    Directory of Open Access Journals (Sweden)

    Yaiza Belacortu

    Full Text Available BACKGROUND: Cabut (Cbt is a C(2H(2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-ß-inducible early-response genes (TIEGs, which belong to Sp1-like/Krüppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and functions are also conserved in the Cbt protein. METHODOLOGY/PRINCIPAL FINDINGS: To determine the transcriptional regulatory activity of the Drosophila Cbt protein, we performed Gal4-based luciferase assays in S2 cells and showed that Cbt is a transcriptional repressor and able to regulate its own expression. Truncated forms of Cbt were then generated to identify its functional domains. This analysis revealed a sequence similar to the mSin3A-interacting repressor domain found in vertebrate TIEGs, although located in a different part of the Cbt protein. Using β-Galactosidase and eGFP fusion proteins, we also showed that Cbt contains the bipartite nuclear localization signal (NLS previously identified in TIEG proteins, although it is non-functional in insect cells. Instead, a monopartite NLS, located at the amino terminus of the protein and conserved across insects, is functional in Drosophila S2 and Spodoptera exigua Sec301 cells. Last but not least, genetic interaction and immunohistochemical assays suggested that Cbt nuclear import is mediated by Importin-α2. CONCLUSIONS/SIGNIFICANCE: Our results constitute the first characterization of the molecular mechanisms of Cbt-mediated transcriptional control as well as of Cbt nuclear import, and demonstrate the

  19. The Drosophila GIPC homologue can modulate myosin based processes and planar cell polarity but is not essential for development.

    Directory of Open Access Journals (Sweden)

    Alexandre Djiane

    Full Text Available Epithelia often show, in addition to the ubiquitous apico-basal (A/B axis, a polarization within the plane of the epithelium, perpendicular to the A/B axis. Such planar cell polarity (PCP is for example evident in the regular arrangement of the stereocilia in the cochlea of the mammalian inner ear or in (almost all Drosophila adult external structures. GIPCs (GAIP interacting protein, C terminus were first identified in mammals and bind to the Galphai GTPase activating protein RGS-GAIP. They have been proposed to act in a G-protein coupled complex controlling vesicular trafficking. Although GIPCs have been found to bind to numerous proteins including Frizzled receptors, which participate in PCP establishment, there is little in vivo evidence for the functional role(s of GIPCs. We show here that overexpressed Drosophila dGIPC alters PCP generation in the wing. We were however unable to find any binding between dGIPC and the Drosophila receptors Fz1 and Fz2. The effect of overexpressed dGIPC is likely due to an effect on the actin cytoskeleton via myosins, since it is almost entirely suppressed by removing a genomic copy of the Myosin VI/jaguar gene. Surprisingly, although dGIPC can interfere with PCP generation and myosin based processes, the complete loss-of-function of dGIPC gives viable adults with no PCP or other detectable defects arguing for a non-essential role of dGIPC in viability and normal Drosophila development.

  20. Midgut-enriched receptor protein tyrosine phosphatase PTP52F is required for Drosophila development during larva-pupa transition.

    Science.gov (United States)

    Santhanam, Abirami; Liang, Suh-Yuen; Chen, Dong-Yuan; Chen, Guang-Chao; Meng, Tzu-Ching

    2013-01-01

    To date our understanding of Drosophila receptor protein tyrosine phosphatases (R-PTPs) in the regulation of signal transduction is limited. Of the seven R-PTPs identified in flies, six are involved in the axon guidance that occurs during embryogenesis. However, whether and how R-PTPs may control key steps of Drosophila development is not clear. In this study we investigated the potential role of Drosophila R-PTPs in developmental processes outside the neuronal system and beyond the embryogenesis stage. Through systematic data mining of available microarray databases, we found the mRNA level of PTP52F to be highly enriched in the midgut of flies at the larva-pupa transition. This finding was confirmed by gut tissue staining with a specific antibody. The unique spatiotemporal expression of PTP52F suggests that it is possibly involved in regulating metamorphosis during the transformation from larva to pupa. To test this hypothesis, we employed RNA interference to examine the defects of transgenic flies. We found that ablation of endogenous PTP52F led to high lethality characterized by the pharate adult phenotype, occurring due to post pupal eclosion failure. These results show that PTP52F plays an indispensable role during the larva-pupa transition. We also found that PTP52F could be reclassified as a member of the subtype R3 PTPs instead of as an unclassified R-PTP without a human ortholog, as suggested previously. Together, these findings suggest that Drosophila R-PTPs may control metamorphosis and other biological processes beyond our current knowledge.

  1. New insights into the ecological interaction between grape berry microorganisms and Drosophila flies during the development of sour rot.

    Science.gov (United States)

    Barata, André; Santos, Sara Correia; Malfeito-Ferreira, Manuel; Loureiro, Virgílio

    2012-08-01

    In this work, we studied the ecological interactions between grape berry microorganisms and Drosophila sp. flies involved in sour rot disease during grape ripening. After veráison the total microbial counts of grape berries affected by sour rot increased from about 2 log CFU/g of berries to more than 7 log CFU/g. Berry damage provoked a clear shift in yeast diversity from basidiomycetes to ascomycetous fermentative species. The latter were mostly Pichia terricola, Hanseniaspora uvarum, Candida zemplinina, and Zygoascus hellenicus. However, these species were not able to produce the metabolites characteristic of sour rot (gluconic and acetic acids) in inoculated berries. On the contrary, the acetic acid bacteria Gluconacetobacter saccharivorans produced high levels of these acids, mainly when berries were incubated in the presence of the insect Drosophila sp. Sour rot was not observed when grape bunches were physically separated from insects, even when berries were artificially injured. The wounds made in berry skin healed in the absence of insects, thus preventing the development of sour rot. Therefore, in the vineyard, the induction of sour rot depends on the contamination of wounded berries by a microbial consortium--yeasts and acetic acid bacteria--transported by drosophilid insects which disseminate sour rot among damaged berries. In the absence of these insects, plant defense mechanisms are effective and lead to skin healing, preventing disease spread. Thus, we showed that Drosophila sp. act as a vector for microorganisms associated with grape sour rot disease.

  2. Minocycline treatment suppresses juvenile development and growth by attenuating insulin/TOR signaling in Drosophila animal model

    Science.gov (United States)

    Yun, Hyun Myoung; Noh, Sujin; Hyun, Seogang

    2017-01-01

    Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner. We found that the drug treatment decreased the activated form of Akt and S6K in peripheral tissues, which suggested that the insulin/target of rapamycin (TOR) signaling had been attenuated. Specifically enhancing TOR activity in the prothoracic gland (PG), the ecdysone-generating organ, attenuated the drug-induced developmental delay, which is consistent with the critical role of PG’s TOR signaling in determining pupation time. Our results reveal previously unrecognized effects of minocycline and offer a new potential therapeutic opportunity for various pathological conditions associated with insulin/TOR signaling. PMID:28317899

  3. The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development

    Directory of Open Access Journals (Sweden)

    Bryan W. Heck

    2011-12-01

    SMRTER (SMRT-related and ecdysone receptor interacting factor is the Drosophila homologue of the vertebrate proteins SMRT and N-CoR, and forms with them a well-conserved family of transcriptional corepressors. Molecular characterization of SMRT-family proteins in cultured cells has implicated them in a wide range of transcriptional regulatory pathways. However, little is currently known about how this conserved class of transcriptional corepressors regulates the development of particular tissues via specific pathways. In this study, through our characterization of multiple Smrter (Smr mutant lines, mosaic analysis of a loss-of-function Smr allele, and studies of two independent Smr RNAi fly lines, we report that SMRTER is required for the development of both ovarian follicle cells and the wing. In these two tissues, SMRTER inhibits not only the ecdysone pathway, but also the Notch pathway. We differentiate SMRTER's influence on these two signaling pathways by showing that SMRTER inhibits the Notch pathway, but not the ecdysone pathway, in a spatiotemporally restricted manner. We further confirm the likely involvement of SMRTER in the Notch pathway by demonstrating a direct interaction between SMRTER and Suppressor of Hairless [Su(H], a DNA-binding transcription factor pivotal in the Notch pathway, and the colocalization of both proteins at many chromosomal regions in salivary glands. Based on our results, we propose that SMRTER regulates the Notch pathway through its association with Su(H, and that overcoming a SMRTER-mediated transcriptional repression barrier may represent a key mechanism used by the Notch pathway to control the precise timing of events and the formation of sharp boundaries between cells in multiple tissues during development.

  4. Early development of the aplacophoran mollusc Chaetoderma

    DEFF Research Database (Denmark)

    Nielsen, Claus; Haszprunar, Gerhard; Ruthensteiner, Bernhard;

    2007-01-01

    The early development of the trochophore larva of the aplacophoran Chaetoderma nitidulum (Mollusca: Caudofoveata = Chaetodermomorpha) is described using scanning and transmission electron microscopy and using fluorescence staining and confocal laser scanning microscopy of the muscle system...... of the early anlagen of the circular body wall muscles does not show the anterior-posterior mode of formation that is typical for annelids, thus strengthening the hypothesis of a non-segmented ancestry of Mollusca....

  5. Psychomotor Behavior: A Practical Approach in Drosophila

    OpenAIRE

    Iliadi, Konstantin G.; Gluscencova, Oxana B.; Boulianne, Gabrielle L

    2016-01-01

    Psychomotor behaviors are governed by fine relationships between physical activity and cognitive functions. Disturbances in psychomotor development and performance are a hallmark of many mental illnesses and often appear as observable and measurable behaviors. Here, we describe a new method called an “equilibrist test,” which can be used to quantify psychomotor learning and performance in Drosophila. We also show how this test can be used to quantify motor disturbances at relatively early sta...

  6. Early Brain Development Research Review and Update

    Science.gov (United States)

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  7. Early development of the human pelvic diaphragm

    NARCIS (Netherlands)

    Koch, Wijnandus Franciscus Robertus Maria

    2006-01-01

    The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methods Use was made of 38 human embryos and fetus

  8. Early development of the human pelvic diaphragm

    NARCIS (Netherlands)

    Koch, Wijnandus Franciscus Robertus Maria

    2006-01-01

    The last decade an increasing interest in the pelvic floor can be observed in medical sciences. The lack of data on the development of the human pelvic floor is striking. The early development of the human pelvic diaphragm was studied. Materials and methodsUse was made of 38 human embryos and

  9. Teacher Knowledge Development in Early Field Experiences

    Science.gov (United States)

    Ingersoll, Casey; Jenkins, Jayne M.; Lux, Karen

    2014-01-01

    Investigation of physical education preservice teacher knowledge development has been primarily limited to study of a single semester of early field experience (EFE), with findings from these investigations driving EFE design. The purpose of this research was to investigate what types of knowledge develop and how knowledge evolves and interacts to…

  10. Early Brain Development Research Review and Update

    Science.gov (United States)

    Schiller, Pam

    2010-01-01

    Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

  11. Transcriptome Encyclopedia of Early Human Development.

    Science.gov (United States)

    Sahakyan, Anna; Plath, Kathrin

    2016-05-01

    Our understanding of human pre-implantation development is limited by the availability of human embryos and cannot completely rely on mouse studies. Petropoulos et al. now provide an extensive transcriptome analysis of a large number of human pre-implantation embryos at single-cell resolution, revealing previously unrecognized features unique to early human development.

  12. Fermitins, the orthologs of mammalian Kindlins, regulate the development of a functional cardiac syncytium in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    James H Catterson

    Full Text Available The vertebrate Kindlins are an evolutionarily conserved family of proteins critical for integrin signalling and cell adhesion. Kindlin-2 (KIND2 is associated with intercalated discs in mice, suggesting a role in cardiac syncytium development; however, deficiency of Kind2 leads to embryonic lethality. Morpholino knock-down of Kind2 in zebrafish has a pleiotropic effect on development that includes the heart. It therefore remains unclear whether cardiomyocyte Kind2 expression is required for cardiomyocyte junction formation and the development of normal cardiac function. To address this question, the expression of Fermitin 1 and Fermitin 2 (Fit1, Fit2, the two Drosophila orthologs of Kind2, was silenced in Drosophila cardiomyocytes. Heart development was assessed in adult flies by immunological methods and videomicroscopy. Silencing both Fit1 and Fit2 led to a severe cardiomyopathy characterised by the failure of cardiomyocytes to develop as a functional syncytium and loss of synchrony between cardiomyocytes. A null allele of Fit1 was generated but this had no impact on the heart. Similarly, the silencing of Fit2 failed to affect heart function. In contrast, the silencing of Fit2 in the cardiomyocytes of Fit1 null flies disrupted syncytium development, leading to severe cardiomyopathy. The data definitively demonstrate a role for Fermitins in the development of a functional cardiac syncytium in Drosophila. The findings also show that the Fermitins can functionally compensate for each other in order to control syncytium development. These findings support the concept that abnormalities in cardiomyocyte KIND2 expression or function may contribute to cardiomyopathies in humans.

  13. The labial gene is required to terminate proliferation of identified neuroblasts in postembryonic development of the Drosophila brain

    Directory of Open Access Journals (Sweden)

    Philipp A. Kuert

    2012-08-01

    The developing brain of Drosophila has become a useful model for studying the molecular genetic mechanisms that give rise to the complex neuronal arrays that characterize higher brains in other animals including mammals. Brain development in Drosophila begins during embryogenesis and continues during a subsequent postembryonic phase. During embryogenesis, the Hox gene labial is expressed in the developing tritocerebrum, and labial loss-of-function has been shown to be associated with a loss of regional neuronal identity and severe patterning defects in this part of the brain. However, nothing is known about the expression and function of labial, or any other Hox gene, during the postembryonic phase of brain development, when the majority of the neurons in the adult brain are generated. Here we report the first analysis of Hox gene action during postembryonic brain development in Drosophila. We show that labial is expressed initially in six larval brain neuroblasts, of which only four give rise to the labial expressing neuroblast lineages present in the late larval brain. Although MARCM-based clonal mutation of labial in these four neuroblast lineages does not result in an obvious phenotype, a striking and unexpected effect of clonal labial loss-of-function does occur during postembryonic brain development, namely the formation of two ectopic neuroblast lineages that are not present in wildtype brains. The same two ectopic neuroblast lineages are also observed following cell death blockage and, significantly, in this case the resulting ectopic lineages are Labial-positive. These findings imply that labial is required in two specific neuroblast lineages of the wildtype brain for the appropriate termination of proliferation through programmed cell death. Our analysis of labial function reveals a novel cell autonomous role of this Hox gene in shaping the lineage architecture of the brain during postembryonic development.

  14. Context- and dose-dependent modulatory effects of naringenin on survival and development of Drosophila melanogaster.

    Science.gov (United States)

    Chattopadhyay, Debarati; Sen, Soumadeep; Chatterjee, Rishita; Roy, Debasish; James, Joel; Thirumurugan, Kavitha

    2016-04-01

    Naringenin, the predominant bioflavonoid found in grapefruit and tomato has diverse bioactive properties that encompass anti-carcinogenic, anti-inflammatory, anti-atherogenic, anti-estrogenic, anti-hyperlipidemic and anti-hyperglycemic characteristics. Naringenin has not been explored for its pro-longevity traits in fruit flies. Therefore, the current study explores its influence on longevity, fecundity, feeding rate, larval development, resistance to starvation stress and body weight in male and female wild-type Drosophila melanogaster Canton-S flies. Flies were fed with normal and high fat diets respectively. The results implied hormetic effects of naringenin on longevity and development in flies. In flies fed with standard and high fat diets, lower concentrations of naringenin (200 and 400 µM) augmented mean lifespan while higher concentrations (600 and 800 µM) were consistently lethal. However, enhanced longevity seen at 400 µM of naringenin was at the expense of reduced fecundity and food intake in flies. Larvae reared on standard diet having 200 µM of naringenin exhibited elevated pupation and emergence as flies. Eclosion time was hastened in larvae reared on standard diet having 200 µM of naringenin. Female flies fed with a standard diet having 200 and 400 µM of naringenin were more resistant to starvation stress. Reduction in body weight was observed in male and female flies fed with a high fat diet supplemented with 200 and 400 µM of naringenin respectively. Collectively, the results elucidated a context- and dose-dependent hormetic efficacy of naringenin that varied with gender, diet and stage of lifecycle in flies.

  15. Optogenetic pacing in Drosophila models (Conference Presentation)

    Science.gov (United States)

    Wu, Penghe; Li, Airong; Men, Jing; Tans, Rudolph E.; Zhou, Chao

    2017-02-01

    The Drosophila melanogaster shares many similarities with vertebrates in heart development. Comparison of heart structural and functional characteristic between male and female Drosophila melanogaster at different developmental stages is helpful to understand heart morphogenesis and function for different genders. And also, it opens up the possibility to uncover the role of sex-related genes in heart development. In this longitudinal study, we cultured and tracked dozens of individually labeled flies throughout their lifecycle. The heart characteristic was measured at different developmental stages during culturing. The gender of each individual fly was determined by adult stage so that the collected data of early stages could be classified to male or female group. We adapted a high-speed optical coherence microscopy (OCM) system with axial and transverse resolution of 2um and 4um, respectively, to perform non-invasive M-mode imaging at a frame rate of 132Hz in Drosophila heart at third instar larva, early pupa and adult stage. Based on those GPU processed M-mode OCM images, we segmented the fly heart region and then quantified the cardiac structural and functional parameters such as heart rate, heart chamber size and so on. Despite large variances of wild type Drosophila in terms of some cardiac characteristic, our results suggest that the heart rate is lower for male flies than for female flies, especially at third instar larva stage. The end diastolic area (EDA) and end systolic area (ESA) of the heart are both slightly larger in female flies than in male flies at larva and adult stage. In summary, we showed gender differences of wild type drosophila in heart functional and structural characteristic.

  16. Early and Late Rate of Force Development

    DEFF Research Database (Denmark)

    Andersen, Lars L; Andersen, Jesper L; Zebis, Mette K

    2010-01-01

    The objective of this study is to investigate the potentially opposing influence of qualitative and quantitative muscular adaptations in response to high-intensity resistance training on contractile rate of force development (RFD) in the early (200 ms) of rising muscle force. Fifteen healthy young...... the vastus lateralis. The main findings were that RFD in the late phase of rising muscle force increased in response to resistance training whereas early RFD remained unchanged and early relative RFD (i.e., RFD/MVC) decreased. Quantitatively, muscle fiber cross-sectional area and MVC increased whereas......-intensity resistance training due to differential influences of qualitative and quantitative muscular adaptations on early and later phases of rising muscle force....

  17. Class I myosins have overlapping and specialized functions in left-right asymmetric development in Drosophila

    National Research Council Canada - National Science Library

    Okumura, Takashi; Sasamura, Takeshi; Inatomi, Momoko; Hozumi, Shunya; Nakamura, Mitsutoshi; Hatori, Ryo; Taniguchi, Kiichiro; Nakazawa, Naotaka; Suzuki, Emiko; Maeda, Reo; Yamakawa, Tomoko; Matsuno, Kenji

    2015-01-01

    .... Drosophila melanogaster has three class I myosin genes, Myosin 31DF (Myo31DF), Myosin 61F (Myo61F), and Myosin 95E (Myo95E). Myo31DF, Myo61F, and Myo95E belong to the Myosin ID, Myosin IC, and Myosin IB families, respectively...

  18. Cell cycle arrest by a gradient of Dpp signaling during Drosophila eye development

    Directory of Open Access Journals (Sweden)

    Bhattacharya Abhishek

    2010-03-01

    Full Text Available Abstract Background The secreted morphogen Dpp plays important roles in spatial regulation of gene expression and cell cycle progression in the developing Drosophila eye. Dpp signaling is required for timely cell cycle arrest ahead of the morphogenetic furrow as a prelude to differentiation, and is also important for eye disc growth. The dpp gene is expressed at multiple locations in the eye imaginal disc, including the morphogenetic furrow that sweeps across the eye disc as differentiation initiates. Results Studies of Brinker and Dad expression, and of Mad phosphorylation, establish that there is a gradient of Dpp signaling in the eye imaginal disc anterior to the morphogenetic furrow, predominantly in the anterior-posterior axis, and also Dpp signaling at the margins of the disc epithelium and in the dorsal peripodial membrane. Almost all signaling activity seems to spread through the plane of the epithelia, although peripodial epithelium cells can also respond to underlying disc cells. There is a graded requirement for Dpp signaling components for G1 arrest in the eye disc, with more stringent requirements further anteriorly where signaling is lower. The signaling level defines the cell cycle response, because elevated signaling through expression of an activated Thickveins receptor molecule arrested cells at more anterior locations. Very anterior regions of the eye disc were not arrested in response to activated receptor, however, and evidence is presented that expression of the Homothorax protein may contribute to this protection. By contrast to activated Thickveins, ectopic expression of processed Dpp leads to very high levels of Mad phosphorylation which appear to have non-physiological consequences. Conclusions G1 arrest occurs at a threshold level of Dpp signaling within a morphogen gradient in the anterior eye. G1 arrest is specific for one competent domain in the eye disc, allowing Dpp signaling to promote growth at earlier

  19. RFamide peptides in early vertebrate development

    Directory of Open Access Journals (Sweden)

    Guro Katrine Sandvik

    2014-12-01

    Full Text Available RFamides (RFa are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play.

  20. Early executive function predicts reasoning development.

    Science.gov (United States)

    Richland, Lindsey E; Burchinal, Margaret R

    2013-01-01

    Analogical reasoning is a core cognitive skill that distinguishes humans from all other species and contributes to general fluid intelligence, creativity, and adaptive learning capacities. Yet its origins are not well understood. In the study reported here, we analyzed large-scale longitudinal data from the Study of Early Child Care and Youth Development to test predictors of growth in analogical-reasoning skill from third grade to adolescence. Our results suggest an integrative resolution to the theoretical debate regarding contributory factors arising from smaller-scale, cross-sectional experiments on analogy development. Children with greater executive-function skills (both composite and inhibitory control) and vocabulary knowledge in early elementary school displayed higher scores on a verbal analogies task at age 15 years, even after adjusting for key covariates. We posit that knowledge is a prerequisite to analogy performance, but strong executive-functioning resources during early childhood are related to long-term gains in fundamental reasoning skills.

  1. Early Phonological Development: Creating an Assessment Test

    Science.gov (United States)

    Stoel-Gammon, Carol; Williams, A. Lynn

    2013-01-01

    This paper describes a new protocol for assessing the phonological systems of two-year-olds with typical development and older children with delays in vocabulary acquisition. The test (Profiles of Early Expressive Phonological Skills ("PEEPS"), Williams & Stoel-Gammon, in preparation) differs from currently available assessments in…

  2. Computer simulation of early embryonic development

    NARCIS (Netherlands)

    Bezem, J.J.; Raven, Chr.P.

    1975-01-01

    A simple model, formulated in terms of elementary geometry, is presented, describing the early development of Lymnaea stagnalis. It includes the main morphogenetic processes active at this stage: cell division, cell flattening and differentiation. Though the model has been designed primarily to fit

  3. The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development.

    Directory of Open Access Journals (Sweden)

    Hélène Chanut-Delalande

    Full Text Available BACKGROUND: Endocytosis is a key regulatory step of diverse signalling pathways, including receptor tyrosine kinase (RTK signalling. Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will subsequently be degraded in lysosomes. It has been well established ex vivo and during Drosophila embryogenesis that Hrs promotes EGFR down regulation. We have recently isolated the first mutations of stam in flies and shown that Stam is required for air sac morphogenesis, a larval respiratory structure whose formation critically depends on finely tuned levels of FGFR activity. This suggest that Stam, putatively within the ESCRT-0 complex, modulates FGF signalling, a possibility that has not been examined in Drosophila yet. PRINCIPAL FINDINGS: Here, we assessed the role of the Hrs/Stam complex in the regulation of signalling activity during Drosophila development. We show that stam and hrs are required for efficient FGFR signalling in the tracheal system, both during cell migration in the air sac primordium and during the formation of fine cytoplasmic extensions in terminal cells. We find that stam and hrs mutant cells display altered FGFR/Btl localisation, likely contributing to impaired signalling levels. Electron microscopy analyses indicate that endosome maturation is impaired at distinct steps by hrs and stam mutations. These somewhat unexpected results prompted us to further explore the function of stam and hrs in EGFR signalling. We show that while stam and hrs together downregulate EGFR signalling in the embryo, they are required for full activation of EGFR signalling during wing development. CONCLUSIONS/SIGNIFICANCE: Our study shows that the ESCRT-0 complex differentially regulates RTK signalling, either positively or negatively depending on tissues and developmental stages, further highlighting the importance of endocytosis in modulating signalling pathways during development.

  4. Genome-wide DNA binding pattern of the homeodomain transcription factor Sine oculis (So in the developing eye of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Barbara Jusiak

    2014-12-01

    Full Text Available The eye of the fruit fly Drosophila melanogaster provides a highly tractable genetic model system for the study of animal development, and many genes that regulate Drosophila eye formation have homologs implicated in human development and disease. Among these is the homeobox gene sine oculis (so, which encodes a homeodomain transcription factor (TF that is both necessary for eye development and sufficient to reprogram a subset of cells outside the normal eye field toward an eye fate. We have performed a genome-wide analysis of So binding to DNA prepared from developing Drosophila eye tissue in order to identify candidate direct targets of So-mediated transcriptional regulation, as described in our recent article [20]. The data are available from NCBI Gene Expression Omnibus (GEO with the accession number GSE52943. Here we describe the methods, data analysis, and quality control of our So ChIP-seq dataset.

  5. Isolation of Drosophila egg chambers for imaging.

    Science.gov (United States)

    Parton, Richard M; Vallés, Ana Maria; Dobbie, Ian M; Davis, Ilan

    2010-04-01

    The fruit fly Drosophila melanogaster is an important model for basic research into the molecular mechanisms underlying cell function and development, as well as a major biomedical research tool. A significant advantage of Drosophila is the ability to apply live cell imaging to a variety of living tissues that can be dissected and imaged in vivo, ex vivo, or in vitro. Drosophila egg chambers, for example, have proven to be a useful model system for studying border cell migration, Golgi unit transport, the rapid movement of mRNA and protein particles, and the role of microtubules in meiosis and oocyte differentiation. A crucial first step before imaging is preparation of the experimental material to ensure physiological relevance and to achieve the best conditions for image quality. Early- to mid-stage egg chambers cannot be mounted in an aqueous-based medium, because this causes a change in microtubule organization and follicle cell morphology. Such egg chambers survive better in Halocarbon oil, which allows free diffusion of oxygen, has low viscosity, and thus prevents dehydration and hypoxia. With a refractive index similar to glycerol, Halocarbon oil also has good optical properties for imaging. It also provides a good environment for injection and is particularly useful for long-term imaging of embryos. However, unlike with aqueous solutions, changes in the medium are not possible. This protocol describes the isolation of Drosophila egg chambers.

  6. Drosophila S2 cells are non-permissive for vaccinia virus DNA replication following entry via low pH-dependent endocytosis and early transcription.

    Directory of Open Access Journals (Sweden)

    Zain Bengali

    Full Text Available Vaccinia virus (VACV, a member of the chordopox subfamily of the Poxviridae, abortively infects insect cells. We have investigated VACV infection of Drosophila S2 cells, which are useful for protein expression and genome-wide RNAi screening. Biochemical and electron microscopic analyses indicated that VACV entry into Drosophila S2 cells depended on the VACV multiprotein entry-fusion complex but appeared to occur exclusively by a low pH-dependent endocytic mechanism, in contrast to both neutral and low pH entry pathways used in mammalian cells. Deep RNA sequencing revealed that the entire VACV early transcriptome, comprising 118 open reading frames, was robustly expressed but neither intermediate nor late mRNAs were made. Nor was viral late protein synthesis or inhibition of host protein synthesis detected by pulse-labeling with radioactive amino acids. Some reduction in viral early proteins was noted by Western blotting. Nevertheless, synthesis of the multitude of early proteins needed for intermediate gene expression was demonstrated by transfection of a plasmid containing a reporter gene regulated by an intermediate promoter. In addition, expression of a reporter gene with a late promoter was achieved by cotransfection of intermediate genes encoding the late transcription factors. The requirement for transfection of DNA templates for intermediate and late gene expression indicated a defect in viral genome replication in VACV-infected S2 cells, which was confirmed by direct analysis. Furthermore, VACV-infected S2 cells did not support the replication of a transfected plasmid, which occurs in mammalian cells and is dependent on all known viral replication proteins, indicating a primary restriction of DNA synthesis.

  7. Proteolytic Processing as a Regulator of BMP-type Signaling in Drosophila Development

    OpenAIRE

    2013-01-01

    A small set of highly conserved signaling molecules performs a great number of tasks in different animals and developmental contexts. Among them, the bone morphogenetic proteins (BMPs) constitute a group of growth and differentiation factors that are involved in numerous developmental processes affecting cell proliferation, apoptosis and differentiation. In the fruit fly, Drosophila melanogaster, three BMP type proteins have been identified, each of which has a homolog in mammals. Decapentapl...

  8. Three-Dimensional Genome Organization and Function in Drosophila.

    Science.gov (United States)

    Schwartz, Yuri B; Cavalli, Giacomo

    2017-01-01

    Understanding how the metazoan genome is used during development and cell differentiation is one of the major challenges in the postgenomic era. Early studies in Drosophila suggested that three-dimensional (3D) chromosome organization plays important regulatory roles in this process and recent technological advances started to reveal connections at the molecular level. Here we will consider general features of the architectural organization of the Drosophila genome, providing historical perspective and insights from recent work. We will compare the linear and spatial segmentation of the fly genome and focus on the two key regulators of genome architecture: insulator components and Polycomb group proteins. With its unique set of genetic tools and a compact, well annotated genome, Drosophila is poised to remain a model system of choice for rapid progress in understanding principles of genome organization and to serve as a proving ground for development of 3D genome-engineering techniques. Copyright © 2017 Schwartz and Cavalli.

  9. Three-Dimensional Genome Organization and Function in Drosophila

    Science.gov (United States)

    Schwartz, Yuri B.; Cavalli, Giacomo

    2017-01-01

    Understanding how the metazoan genome is used during development and cell differentiation is one of the major challenges in the postgenomic era. Early studies in Drosophila suggested that three-dimensional (3D) chromosome organization plays important regulatory roles in this process and recent technological advances started to reveal connections at the molecular level. Here we will consider general features of the architectural organization of the Drosophila genome, providing historical perspective and insights from recent work. We will compare the linear and spatial segmentation of the fly genome and focus on the two key regulators of genome architecture: insulator components and Polycomb group proteins. With its unique set of genetic tools and a compact, well annotated genome, Drosophila is poised to remain a model system of choice for rapid progress in understanding principles of genome organization and to serve as a proving ground for development of 3D genome-engineering techniques. PMID:28049701

  10. Nurturing care: promoting early childhood development.

    Science.gov (United States)

    Britto, Pia R; Lye, Stephen J; Proulx, Kerrie; Yousafzai, Aisha K; Matthews, Stephen G; Vaivada, Tyler; Perez-Escamilla, Rafael; Rao, Nirmala; Ip, Patrick; Fernald, Lia C H; MacMillan, Harriet; Hanson, Mark; Wachs, Theodore D; Yao, Haogen; Yoshikawa, Hirokazu; Cerezo, Adrian; Leckman, James F; Bhutta, Zulfiqar A

    2017-01-07

    The UN Sustainable Development Goals provide a historic opportunity to implement interventions, at scale, to promote early childhood development. Although the evidence base for the importance of early childhood development has grown, the research is distributed across sectors, populations, and settings, with diversity noted in both scope and focus. We provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection. Our review concludes that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care. The recommendations emphasise that intervention packages should be applied at developmentally appropriate times during the life course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence now strongly suggests that parents, caregivers, and families need to be supported in providing nurturing care and protection in order for young children to achieve their developmental potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Receptor-type guanylyl cyclase Gyc76C is required for development of the Drosophila embryonic somatic muscle

    Directory of Open Access Journals (Sweden)

    Unisha Patel

    2012-04-01

    Guanylyl cyclases mediate a number of physiological processes, including smooth muscle function and axonal guidance. Here, we report a novel role for Drosophila receptor-type guanylyl cyclase at 76C, Gyc76C, in development of the embryonic somatic muscle. In embryos lacking function of Gyc76C or the downstream cGMP-dependent protein kinase (cGK, DG1, patterning of the somatic body wall muscles was abnormal with ventral and lateral muscle groups showing the most severe defects. In contrast, specification and elongation of the dorsal oblique and dorsal acute muscles of gyc76C mutant embryos was normal, and instead, these muscles showed defects in proper formation of the myotendinous junctions (MTJs. During MTJ formation in gyc76C and pkg21D mutant embryos, the βPS integrin subunit failed to localize to the MTJs and instead was found in discrete puncta within the myotubes. Tissue-specific rescue experiments showed that gyc76C function is required in the muscle for proper patterning and βPS integrin localization at the MTJ. These studies provide the first evidence for a requirement for Gyc76C and DG1 in Drosophila somatic muscle development, and suggest a role in transport and/or retention of integrin receptor subunits at the developing MTJs.

  12. Early development and regression in Rett syndrome.

    Science.gov (United States)

    Lee, J Y L; Leonard, H; Piek, J P; Downs, J

    2013-12-01

    This study utilized developmental profiling to examine symptoms in 14 girls with genetically confirmed Rett syndrome and whose families were participating in the Australian Rett syndrome or InterRett database. Regression was mostly characterized by loss of hand and/or communication skills (13/14) except one girl demonstrated slowing of skill development. Social withdrawal and inconsolable crying often developed simultaneously (9/14), with social withdrawal for shorter duration than inconsolable crying. Previously acquired gross motor skills declined in just over half of the sample (8/14), mostly observed as a loss of balance. Early abnormalities such as vomiting and strabismus were also seen. Our findings provide additional insight into the early clinical profile of Rett syndrome.

  13. The developing hypopharyngeal microbiota in early life

    DEFF Research Database (Denmark)

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael

    2016-01-01

    BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establi......BACKGROUND: The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand...... the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. RESULTS: Our analysis shows...

  14. Cytoskeleton and Early Development in Fucoid Algae

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Cell polarization and asymmetric cell divisions play important roles during development in many multicellular eukaryotes.Fucoid algae have a long history as models for studying early developmental processes, probably because of the ease with which zygotes can be observed and manipulated in the laboratory. This review discusses cell polarization and asymmetric cell divisions in fucoid algal zygotes with an emphasis on the roles played by the cytoskeleton.

  15. QCD development in the early universe

    Energy Technology Data Exchange (ETDEWEB)

    Gromov, N. A., E-mail: gromov@dm.komisc.ru [Komi Science Center of the Ural Division of the Russian Academy of Sciences, Department of Mathematics (Russian Federation)

    2017-03-15

    The high-energy limit of Quantum Chromodynamics is generated by the contraction of its gauge groups. Contraction parameters are taken identical with those of the Electroweak Model and tend to zero when energy increases. At the infinite energy limit all quarks lose masses and have only one color degree of freedom. The limit model represents the development of Quantum Chromodynamics in the early Universe from the Big Bang up to the end of several milliseconds.

  16. [Temperature control of the crossing-over frequency in Drosophila melanogaster. Effect of infra- and super-optimal shock temperatures in early ontogenesis on the recombination frequency].

    Science.gov (United States)

    Grushko, T A; Korochkina, S E; Klimenko, V V

    1991-10-01

    Effect of temperature shock treatments (0 and 37 degrees C) in early ontogenesis on recombination frequency was studied in two strains of Drosophila X1 and X2. Recombination frequency under treatment with temperature of 0 degrees C and 37 degrees C (shock treatment), as well as at 14 degrees C and 29 degrees C nonshock treatment was found to be dependent on strain genotype, the chromosomal segments under consideration, developmental stage and the age of individuals analysed. Shock treatments usually increase recombination frequency, whereas nonshock treatments lead to unstable and variable recombination frequencies. A concept of ontogenic homeostasis of recombination has been introduced. It is assumed that the effect of temperature treatments on recombination frequency is indirect--i.e. physiologically mediated.

  17. Drosophila Shep and C. elegans SUP-26 are RNA-binding proteins that play diverse roles in nervous system development.

    Science.gov (United States)

    Schachtner, Logan T; Sola, Ismail E; Forand, Daniel; Antonacci, Simona; Postovit, Adam J; Mortimer, Nathan T; Killian, Darrell J; Olesnicky, Eugenia C

    2015-11-01

    The Caenorhabditis elegans gene sup-26 encodes a well-conserved RNA-recognition motif-containing RNA-binding protein (RBP) that functions in dendrite morphogenesis of the PVD sensory neuron. The Drosophila ortholog of sup-26, alan shepard (shep), is expressed throughout the nervous system and has been shown to regulate neuronal remodeling during metamorphosis. Here, we extend these studies to show that sup-26 and shep are required for the development of diverse cell types within the nematode and fly nervous systems during embryonic and larval stages. We ascribe roles for sup-26 in regulating dendrite number and the expression of genes involved in mechanosensation within the nematode peripheral nervous system. We also find that in Drosophila, shep regulates dendrite length and branch order of nociceptive neurons, regulates the organization of neuronal clusters of the peripheral nervous system and the organization of axons within the ventral nerve cord. Taken together, our results suggest that shep/sup-26 orthologs play diverse roles in neural development across animal species. Moreover, we discuss potential roles for shep/sup-26 orthologs in the human nervous system.

  18. Quantitative Measurement of Histone Tail Acetylation Reveals Stage-Specific Regulation and Response to Environmental Changes during Drosophila Development.

    Science.gov (United States)

    Henry, Ryan A; Singh, Tanu; Kuo, Yin-Ming; Biester, Alison; O'Keefe, Abigail; Lee, Sandy; Andrews, Andrew J; O'Reilly, Alana M

    2016-03-22

    Histone modification plays a major role in regulating gene transcription and ensuring the healthy development of an organism. Numerous studies have suggested that histones are dynamically modified during developmental events to control gene expression levels in a temporal and spatial manner. However, the study of histone acetylation dynamics using currently available techniques is hindered by the difficulty of simultaneously measuring acetylation of the numerous potential sites of modification present in histones. Here, we present a methodology that allows us to combine mass spectrometry-based histone analysis with Drosophila developmental genetics. Using this system, we characterized histone acetylation patterns during multiple developmental stages of the fly. Additionally, we utilized this analysis to characterize how treatments with pharmacological agents or environmental changes such as γ-irradiation altered histone acetylation patterns. Strikingly, γ-irradiation dramatically increased the level of acetylation at H3K18, a site linked to DNA repair via nonhomologous end joining. In mutant fly strains deficient in DNA repair proteins, however, this increase in the level of H3K18 acetylation was lost. These results demonstrate the efficacy of our combined mass spectrometry system with a Drosophila model system and provide interesting insight into the changes in histone acetylation during development, as well as the effects of both pharmacological and environmental agents on global histone acetylation.

  19. Transient Dysregulation of Dopamine Signaling in a Developing Drosophila Arousal Circuit Permanently Impairs Behavioral Responsiveness in Adults

    Science.gov (United States)

    Ferguson, Lachlan; Petty, Alice; Rohrscheib, Chelsie; Troup, Michael; Kirszenblat, Leonie; Eyles, Darryl W.; van Swinderen, Bruno

    2017-01-01

    The dopamine ontogeny hypothesis for schizophrenia proposes that transient dysregulation of the dopaminergic system during brain development increases the likelihood of this disorder in adulthood. To test this hypothesis in a high-throughput animal model, we have transiently manipulated dopamine signaling in the developing fruit fly Drosophila melanogaster and examined behavioral responsiveness in adult flies. We found that either a transient increase of dopamine neuron activity or a transient decrease of dopamine receptor expression during fly brain development permanently impairs behavioral responsiveness in adults. A screen for impaired responsiveness revealed sleep-promoting neurons in the central brain as likely postsynaptic dopamine targets modulating these behavioral effects. Transient dopamine receptor knockdown during development in a restricted set of ~20 sleep-promoting neurons recapitulated the dopamine ontogeny phenotype, by permanently reducing responsiveness in adult animals. This suggests that disorders involving impaired behavioral responsiveness might result from defective ontogeny of sleep/wake circuits. PMID:28243212

  20. Expression of nebulette during early cardiac development.

    Science.gov (United States)

    Esham, Michael; Bryan, Kourtney; Milnes, Jennifer; Holmes, William B; Moncman, Carole L

    2007-04-01

    Nebulette, a cardiac homologue of nebulin, colocalizes with alpha-actinin in the pre-myofibrils of spreading cardiomyocytes and has been hypothesized to play a critical role in the formation of the thin-filament-Z-line complex early during myofibrillogenesis. Data from mesodermal explants or whole tissue mounts of developing hearts suggest that the pattern of myofibrillogenesis in situ may differ from observations of spreading cardiomyocytes. To evaluate the role of nebulette in myofibrillogenesis, we have analyzed the expression of nebulette in chicken heart rudiments by immunoblots and immunofluorescence. We detect the 110 kDa nebulette in heart rudiments derived from stage 9-10 using the anti-nebulin mAb, N114, or polyclonal anti-nebulette Abs by immunoblotting. Immunofluorescence analysis of explants stained with anti-nebulette and anti-alpha-actinin Abs demonstrates that both proteins localize along actin filaments in punctate to continuous manner at early stages of cardiac development and later give rise to striations. In both cases, the punctate staining had a periodicity of approximately 1.0 microm indicating a pre-myofibrils distribution at the earliest time points examined. We demonstrate that nebulette is indeed associated with premyofibrils in very early stages of myofibrillogenesis and suggest that nebulette may play an important role in the formation of these structures.

  1. Cognitive theories of early gender development.

    Science.gov (United States)

    Martin, Carol Lynn; Ruble, Diane N; Szkrybalo, Joel

    2002-11-01

    The contribution of cognitive perspectives (cognitive-developmental theory and gender schema theory) to a contemporary understanding of gender development is evaluated. Recent critiques of cognitive approaches are discussed and empirical evidence is presented to counter these critiques. Because of the centrality of early gender development to the cognitive perspective, the latest research is reviewed on how infants and toddlers discriminate the sexes and learn the attributes correlated with sex. The essence of cognitive approaches--emphasis on motivational consequences of gender concepts; the active, self-initiated view of development; and focus on developmental patterns-is highlighted and contrasted with social-cognitive views. The value of cognitive theories to the field is illustrated, and recommendations are made concerning how to construct comprehensive, integrative perspectives of gender development.

  2. Photobiomodulation of early mouse embryo development

    Science.gov (United States)

    Sviridova-Chailakhyan, T. A.; Fakhranurova, L. I.; Simonova, N. B.; Khramov, R. N.; Manokhin, A. A.; Paskevich, S. I.; Chailakhyan, L. M.

    2008-04-01

    The effect of artificial sunlight (AS) from a xenon source and of converted AS with an additional orange-red luminescent (λ MAX=626 nm) component (AS+L) on the development of mouse zygotes was investigated. A plastic screen with a photoluminophore layer was used for production of this orange-red luminescent (L) component. A single short-term (15 min) exposure produced a long-term stable positive effect on early embryo development of mice, which persisted during several days. After exposure to AS+L, a stimulating influence on preimplantation development was observed, in comparison with the control group without AS exposure. The positive effects were as follows: increase in percent of embryos (P <= 0.05) developed to the blastocyst stage (96.2 %) with hatching from the zona pellucida (80.8 %) within 82-96 hours in vitro compared to the control (67.1 % and 28.8 %, respectively).

  3. ROCK inhibition prevents early mouse embryo development.

    Science.gov (United States)

    Duan, Xing; Chen, Kun-Lin; Zhang, Yu; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    ROCK is a Rho-GTPase effector that is important for actin assembly and is involved in various cellular functions, including cell contraction, migration, motility, and tumor cell invasion. In this study, we investigated ROCK expression and function during early mouse embryo development. Inhibiting ROCK by Y-27632 treatment at the zygote stage resulted in first cleavage failure, and most embryos failed to develop to the 8-cell stage. When adding Y-27632 at the 8-cell stage, embryos failed to undergo compaction and could not develop into blastocysts. In addition, fluorescence staining intensity analysis indicated that actin expression at blastomere membranes was significantly reduced. After ROCK inhibition, two or more nuclei were observed in a cell, which indicated possible cytokinesis failure. Moreover, after ROCK inhibition with Y-27632, the phosphorylation levels of LIMK1/2, a downstream molecule of ROCK, were decreased at blastomere membranes. Thus, our results showed conserved roles for ROCK in this mammalian embryo model and indicated that a ROCK-LIMK1/2-actin pathway might regulate cleavage and blastocyst formation during early mouse embryo development.

  4. Unc-51/ATG1 controls axonal and dendritic development via kinesin-mediated vesicle transport in the Drosophila brain.

    Directory of Open Access Journals (Sweden)

    Hiroaki Mochizuki

    Full Text Available BACKGROUND: Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II, an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM and No distributive disjunction (Nod, remains unaltered. Genetic analyses of kinesin light chain (Klc and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations. CONCLUSIONS/SIGNIFICANCE: Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules

  5. The developing hypopharyngeal microbiota in early life.

    Science.gov (United States)

    Mortensen, Martin Steen; Brejnrod, Asker Daniel; Roggenbuck, Michael; Abu Al-Soud, Waleed; Balle, Christina; Krogfelt, Karen Angeliki; Stokholm, Jakob; Thorsen, Jonathan; Waage, Johannes; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren Johannes

    2016-12-30

    The airways of healthy humans harbor a distinct microbial community. Perturbations in the microbial community have been associated with disease, yet little is known about the formation and development of a healthy airway microbiota in early life. Our goal was to understand the establishment of the airway microbiota within the first 3 months of life. We investigated the hypopharyngeal microbiota in the unselected COPSAC2010 cohort of 700 infants, using 16S rRNA gene sequencing of hypopharyngeal aspirates from 1 week, 1 month, and 3 months of age. Our analysis shows that majority of the hypopharyngeal microbiota of healthy infants belong to each individual's core microbiota and we demonstrate five distinct community pneumotypes. Four of these pneumotypes are dominated by the genera Staphylococcus, Streptococcus, Moraxella, and Corynebacterium, respectively. Furthermore, we show temporal pneumotype changes suggesting a rapid development towards maturation of the hypopharyngeal microbiota and a significant effect from older siblings. Despite an overall common trajectory towards maturation, individual infants' microbiota are more similar to their own, than to others, over time. Our findings demonstrate a consolidation of the population of indigenous bacteria in healthy airways and indicate distinct trajectories in the early development of the hypopharyngeal microbiota.

  6. Bruchpilot in ribbon-like axonal agglomerates, behavioral defects, and early death in SRPK79D kinase mutants of Drosophila.

    Directory of Open Access Journals (Sweden)

    Vanessa Nieratschker

    2009-10-01

    Full Text Available Defining the molecular structure and function of synapses is a central theme in brain research. In Drosophila the Bruchpilot (BRP protein is associated with T-shaped ribbons ("T-bars" at presynaptic active zones (AZs. BRP is required for intact AZ structure and normal evoked neurotransmitter release. By screening for mutations that affect the tissue distribution of Bruchpilot, we have identified a P-transposon insertion in gene CG11489 (location 79D which shows high homology to mammalian genes for SR protein kinases (SRPKs. SRPKs phosphorylate serine-arginine rich splicing factors (SR proteins. Since proteins expressed from CG11489 cDNAs phosphorylate a peptide from a human SR protein in vitro, we name CG11489 the Drosophila Srpk79D gene. We have characterized Srpk79D transcripts and generated a null mutant. Mutation of the Srpk79D gene causes conspicuous accumulations of BRP in larval and adult nerves. At the ultrastructural level, these correspond to extensive axonal agglomerates of electron-dense ribbons surrounded by clear vesicles. Basic synaptic structure and function at larval neuromuscular junctions appears normal, whereas life expectancy and locomotor behavior of adult mutants are significantly impaired. All phenotypes of the mutant can be largely or completely rescued by panneural expression of SRPK79D isoforms. Isoform-specific antibodies recognize panneurally overexpressed GFP-tagged SRPK79D-PC isoform co-localized with BRP at presynaptic active zones while the tagged -PB isoform is found in spots within neuronal perikarya. SRPK79D concentrations in wild type apparently are too low to be revealed by these antisera. We propose that the Drosophila Srpk79D gene characterized here may be expressed at low levels throughout the nervous system to prevent the assembly of BRP containing agglomerates in axons and maintain intact brain function. The discovery of an SR protein kinase required for normal BRP distribution calls for the

  7. Cell proliferation control by Notch signalling during imaginal discs development in Drosophila

    Directory of Open Access Journals (Sweden)

    Carlos Estella

    2015-02-01

    Full Text Available The Notch signalling pathway is evolutionary conserved and participates in numerous developmental processes, including the control of cell proliferation. However, Notch signalling can promote or restrain cell division depending on the developmental context, as has been observed in human cancer where Notch can function as a tumor suppressor or an oncogene. Thus, the outcome of Notch signalling can be influenced by the cross-talk between Notch and other signalling pathways. The use of model organisms such as Drosophila has been proven to be very valuable to understand the developmental role of the Notch pathway in different tissues and its relationship with other signalling pathways during cell proliferation control. Here we review recent studies in Drosophila that shed light in the developmental control of cell proliferation by the Notch pathway in different contexts such as the eye, wing and leg imaginal discs. We also discuss the autonomous and non-autonomous effects of the Notch pathway on cell proliferation and its interactions with different signalling pathways.

  8. Mesodermal Nkx2.5 is necessary and sufficient for early second heart field development.

    Science.gov (United States)

    Zhang, Lu; Nomura-Kitabayashi, Aya; Sultana, Nishat; Cai, Weibin; Cai, Xiaoqiang; Moon, Anne M; Cai, Chen-Leng

    2014-06-01

    The vertebrate heart develops from mesoderm and requires inductive signals secreted from early endoderm. During embryogenesis, Nkx2.5 acts as a key transcription factor and plays essential roles for heart formation from Drosophila to human. In mice, Nkx2.5 is expressed in the early first heart field, second heart field pharyngeal mesoderm, as well as pharyngeal endodermal cells underlying the second heart field. Currently, the specific requirements for Nkx2.5 in the endoderm versus mesoderm with regard to early heart formation are incompletely understood. Here, we performed tissue-specific deletion in mice to dissect the roles of Nkx2.5 in the pharyngeal endoderm and mesoderm. We found that heart development appeared normal after endodermal deletion of Nkx2.5 whereas mesodermal deletion engendered cardiac defects almost identical to those observed on Nkx2.5 null embryos (Nkx2.5(-/-)). Furthermore, re-expression of Nkx2.5 in the mesoderm rescued Nkx2.5(-/-) heart defects. Our findings reveal that Nkx2.5 in the mesoderm is essential while endodermal expression is dispensable for early heart formation in mammals.

  9. The insulator protein Suppressor of Hairy wing is required for proper ring canal development during oogenesis in Drosophila.

    Science.gov (United States)

    Hsu, Shih-Jui; Plata, Maria P; Ernest, Ben; Asgarifar, Saghi; Labrador, Mariano

    2015-07-01

    Chromatin insulators orchestrate gene transcription during embryo development and cell differentiation by stabilizing interactions between distant genomic sites. Mutations in genes encoding insulator proteins are generally lethal, making in vivo functional analyses of insulator proteins difficult. In Drosophila, however, mutations in the gene encoding the Suppressor of Hairy wing insulator protein [Su(Hw)] are viable and female sterile, providing an opportunity to study insulator function during oocyte development. Whereas previous reports suggest that the function of Su(Hw) in oogenesis is independent of its insulator activity, many aspects of the role of Su(Hw) in Drosophila oogenesis remain unexplored. Here we show that mutations in su(Hw) result in smaller ring canal lumens and smaller outer ring diameters, which likely obstruct molecular and vesicle passage from nurse cells to the oocyte. Fluorescence microscopy reveals that lack of Su(Hw) leads to excess accumulation of Kelch (Kel) and Filament-actin (F-actin) proteins in the ring canal structures of developing egg chambers. Furthermore, we found that misexpression of the Src oncogene at 64B (Src64B) may cause ring canal development defects as microarray analysis and real-time RT-PCR revealed there is a three fold decrease in Src64B expression in su(Hw) mutant ovaries. Restoration of Src64B expression in su(Hw) mutant female germ cells rescued the ring phenotype but did not restore fertility. We conclude that loss of su(Hw) affects expression of many oogenesis related genes and down-regulates Src64B, resulting in ring canal defects potentially contributing to obstruction of molecular flow and an eventual failure of egg chamber organization.

  10. A comparative analysis of frog early development.

    Science.gov (United States)

    del Pino, Eugenia M; Venegas-Ferrín, Michael; Romero-Carvajal, Andrés; Montenegro-Larrea, Paola; Sáenz-Ponce, Natalia; Moya, Iván M; Alarcón, Ingrid; Sudou, Norihiro; Yamamoto, Shinji; Taira, Masanori

    2007-07-17

    The current understanding of Xenopus laevis development provides a comparative background for the analysis of frog developmental modes. Our analysis of development in various frogs reveals that the mode of gastrulation is associated with developmental rate and is unrelated to egg size. In the gastrula of the rapidly developing embryos of the foam-nesting frogs Engystomops coloradorum and Engystomops randi, archenteron and notochord elongation overlapped with involution at the blastopore lip, as in X. laevis embryos. In embryos of dendrobatid frogs and in the frog without tadpoles Eleutherodactylus coqui, which develop somewhat more slowly than X. laevis, involution and archenteron elongation concomitantly occurred during gastrulation; whereas elongation of the notochord and, therefore, dorsal convergence and extension, occurred in the postgastrula. In contrast, in the slow developing embryos of the marsupial frog Gastrotheca riobambae, only involution occurred during gastrulation. The processes of archenteron and notochord elongation and convergence and extension were postgastrulation events. We produced an Ab against the homeodomain protein Lim1 from X. laevis as a tool for the comparative analysis of development. By the expression of Lim1, we were able to identify the dorsal side of the G. riobambae early gastrula, which otherwise was difficult to detect. Moreover, the Lim1 expression in the dorsal lip of the blastopore and notochord differed among the studied frogs, indicating variation in the timing of developmental events. The variation encountered gives evidence of the modular character of frog gastrulation.

  11. Vegfa Impacts Early Myocardium Development in Zebrafish

    Science.gov (United States)

    Zhu, Diqi; Fang, Yabo; Gao, Kun; Shen, Jie; Zhong, Tao P.; Li, Fen

    2017-01-01

    Vascular endothelial growth factor A (Vegfa) signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk. PMID:28230770

  12. Vegfa Impacts Early Myocardium Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Diqi Zhu

    2017-02-01

    Full Text Available Vascular endothelial growth factor A (Vegfa signaling regulates cardiovascular development. However, the cellular mechanisms of Vegfa signaling in early cardiogenesis remain poorly understood. The present study aimed to understand the differential functions and mechanisms of Vegfa signaling in cardiac development. A loss-of-function approach was utilized to study the effect of Vegfa signaling in cardiogenesis. Both morphants and mutants for vegfaa display defects in cardiac looping and chamber formation, especially the ventricle. Vegfa regulates the heart morphogenesis in a dose-dependent manner. Furthermore, the initial fusion of the bilateral myocardium population is delayed rather than endocardium. The results demonstrate that Vegfa signaling plays a direct impact on myocardium fusion, indicating that it is the initial cause of the heart defects. The heart morphogenesis is regulated by Vegfa in a dose-dependent manner, and later endocardium defects may be secondary to impaired myocardium–endocardium crosstalk.

  13. Early development of the vertebral column.

    Science.gov (United States)

    Scaal, Martin

    2016-01-01

    The segmental organization of the vertebrate body is most obviously visible in the vertebral column, which consists of a series of vertebral bones and interconnecting joints and ligaments. During embryogenesis, the vertebral column derives from the somites, which are the primary segments of the embryonic paraxial mesoderm. Anatomical, cellular and molecular aspects of vertebral column development have been of interest to developmental biologists for more than 150 years. This review briefly summarizes the present knowledge on early steps of vertebral column development in amniotes, starting from sclerotome formation and leading to the establishment of the anatomical bauplan of the spine composed of vertebral bodies, vertebral arches, intervertebral discs and ribs, and their specific axial identities along the body axis.

  14. The Hsp60C gene in the 25F cytogenetic region in Drosophila melanogaster is essential for tracheal development and fertility

    Indian Academy of Sciences (India)

    Surajit Sarkar; Subhash C. Lakhotia

    2005-12-01

    Earlier studies have shown that of the four genes (Hsp60A, Hsp60B, Hsp60C, Hsp60D genes) predicted to encode the conserved Hsp60 family chaperones in Drosophila melanogaster, the Hsp60A gene (at the 10A polytene region) is expressed in all cell types of the organism and is essential from early embryonic stages, while the Hsp60B gene (at 21D region) is expressed only in testis, being essential for sperm individualization. In the present study, we characterized the Hsp60C gene (at 25F region), which shows high sequence homology with the other three Hsp60 genes of D. melanogaster. In situ hybridization of Hsp60C-specific riboprobe shows that expression of this gene begins in late embryonic stages (stage 14 onwards), particularly in the developing tracheal system and salivary glands; during larval and adult stages, it is widely expressed in many cell types but much more strongly in tracheae and in developing and differentiating germ cells. A P-insertion mutant (Hsp60C1) allele with the P transposon inserted at $-251$ position of the Hsp60C gene promoter was generated. This early larval recessive lethal mutation significantly reduces levels of Hsp60C transcripts in developing tracheae and this is associated with a variety of defects in the tracheal system, including lack of liquid clearance. About 10% of the homozygotes survive as weak, shortlived and completely sterile adults. Testes of the surviving mutant males are significantly smaller, with fewer spermatocytes, most of which do not develop beyond the round spermatid stage. In situ and Northern hybridizations show significantly reduced levels of the Hsp60C transcripts in Hsp60C1 homozygous adult males. The absence of early meiotic stages in the Hsp60C1 homozygous testes contrasts with the effect of testis-specific Hsp60B (21D) gene, whose mutation affects individualization of sperm bundles later in spermiogenesis. In view of the specific effects in tracheal development and in early stages of spermatogenesis, it is

  15. BMAA neurotoxicity in Drosophila.

    Science.gov (United States)

    Zhou, Xianchong; Escala, Wilfredo; Papapetropoulos, Spyridon; Bradley, Walter G; Zhai, R Grace

    2009-01-01

    We report the establishment of an in vivo model using the fruit fly Drosophila melanogaster to investigate the toxic effects of L-BMAA. We found that dietary intake of BMAA reduced the lifespan as well as the neurological functions of flies. Furthermore, we have developed an HPLC method to reliably detect both free and protein-bound BMAA in fly tissue extracts.

  16. Development of Life on Early Mars

    Science.gov (United States)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2009-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

  17. Cell fate regulation in early mammalian development

    Science.gov (United States)

    Oron, Efrat; Ivanova, Natalia

    2012-08-01

    Preimplantation development in mammals encompasses a period from fertilization to implantation and results in formation of a blastocyst composed of three distinct cell lineages: epiblast, trophectoderm and primitive endoderm. The epiblast gives rise to the organism, while the trophectoderm and the primitive endoderm contribute to extraembryonic tissues that support embryo development after implantation. In many vertebrates, such as frog or fish, maternally supplied lineage determinants are partitioned within the egg. Cell cleavage that follows fertilization results in polarization of these factors between the individual blastomeres, which become restricted in their developmental fate. In contrast, the mouse oocyte and zygote lack clear polarity and, until the eight-cell stage, individual blastomeres retain the potential to form all lineages. How are cell lineages specified in the absence of a maternally supplied blueprint? This is a fundamental question in the field of developmental biology. The answer to this question lies in understanding the cell-cell interactions and gene networks involved in embryonic development prior to implantation and using this knowledge to create testable models of the developmental processes that govern cell fates. We provide an overview of classic and contemporary models of early lineage development in the mouse and discuss the emerging body of work that highlights similarities and differences between blastocyst development in the mouse and other mammalian species.

  18. Early Literacy and Early Numeracy: The Value of Including Early Literacy Skills in the Prediction of Numeracy Development

    Science.gov (United States)

    Purpura, David J.; Hume, Laura E.; Sims, Darcey M.; Lonigan, Cristopher J.

    2011-01-01

    The purpose of this study was to examine whether early literacy skills uniquely predict early numeracy skills development. During the first year of the study, 69 3- to 5-year-old preschoolers were assessed on the Preschool Early Numeracy Skills (PENS) test and the Test of Preschool Early Literacy Skills (TOPEL). Participants were assessed again a…

  19. Expression of the Idefix retrotransposon in early follicle cells in the germarium of Drosophila melanogaster is determined by its LTR sequences and a specific genomic context.

    Science.gov (United States)

    Tcheressiz, S; Calco, V; Arnaud, F; Arthaud, L; Dastugue, B; Vaury, C

    2002-04-01

    Retrotransposons are transcriptionally activated in different tissues and cell types by a variety of genomic and environmental factors. Transcription of LTR retrotransposons is controlled by cis-acting regulatory sequences in the 5' LTR. Mobilization of two LTR retroelements, Idefix and ZAM, occurs in the unstable RevI line of Drosophila melanogaster, in which their copy numbers are high, while they are low in all other stocks tested. Here we show that both a full-length and a subgenomic Idefix transcript that are necessary for its mobilization are present in the Rev1 line, but not in the other lines. Studies on transgenic strains demonstrate that the 5' LTR of Idefix contains sequences that direct the tissue-specific expression of the retroelement in testes and ovaries of adult flies. In ovaries, expression occurs in the early follicle and in other somatic cells of the germarium, and is strictly associated with the unstable genetic context conferred by the RevI line. Control of tissue-specific Idefix expression by interactions between cis-acting sequences of its LTR and trans-acting genomic factors provides an opportunity to use this retroelement as a tool for the study of the early follicle cell lineage in the germarium.

  20. Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila

    Directory of Open Access Journals (Sweden)

    Ilaria Drago

    2016-09-01

    Full Text Available The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn—a brain region critical for olfactory memory formation—causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism.

  1. Gene structure of Drosophila diaphorase-1: diversity of transcripts in adult males and females, in different organs and at different stages of development

    Indian Academy of Sciences (India)

    Pavlina M. Ivanova; Boris H. Dunkov; Kiril H. Ralchev

    2008-08-01

    The gene EG:22E5.5 or CG4199 (accession number O77266, Q9W529) from Berkeley Drosophila Genome Project (BDGP) was found using the partial amino acid sequences of three tryptic peptides obtained from purified Drosophila virilis diaphorase-1. This gene is located on the X chromosome at position 2C9–2C10. The structure of the gene reveals three exons and two long introns. Using BDGP, we found six transcripts in this gene. The difference between these transcripts is in their 5′ ends; the 3′ ends of the six transcripts are identical. Thirty-four ESTs from different cDNA libraries were found, most of them from Schneider L2 cell culture (SH) cDNA library. The transcripts are represented at very low level in the cells of different organs and at different stages of Drosophila development. Using RT-PCR, we obtained five of these transcripts in cDNA samples from female adult flies. However, we could not find any of them in cDNA samples from male adult flies. Moreover, we obtained only the third transcript (CG4199-RC) in the sample of testis from adult flies and the fourth transcript (CG4199-RD) in an embryo sample. None of the other five transcripts were found in the samples of different organs and in the samples obtained at different stages of Drosophila development.

  2. Early development of grateloupia turuturu (Halymeniaceae, Rhodophyta)

    Science.gov (United States)

    Wang, Gaoge; Jiang, Chunmei; Wang, Shasha; Wei, Xiaojiao; Zhao, Fengjuan

    2012-03-01

    Grateloupia turuturu is a commercial red alga with potential value in nutraceuticals and pharmaceuticals. To supplement information on its life history and verify whether carpospores can be used for seedling culture, early development of G. turuturu was investigated under culture conditions (27°C, 10-13 μol/(m2·s) in irradiance, photoperiod 10:14 h L:D). Three physiological stages were recognized by continuous microscopic observation: division stage, discoid crust stage, and juvenile seedling stage. At the beginning of the division stage, the carpospores developed germ tubes into which the carpospore protoplasm was evacuated, and then the carpospore protoplasm in the germ tubes began to divide continuously until discoid crusts formed. Finally, upright thalli appeared on the discoid crusts and developed into juvenile seedlings. It took about 60 days for carpospores to develop into juvenile seedlings. The growth parameters, including germination rate for carpospores and discoid crust diameter, were recorded. These results contribute more information on the life cycle, and at the same time are of great significance in the scaling-up of artificial seedling cultures of G. turuturu.

  3. Communication and community development: early child development programs.

    Science.gov (United States)

    Wood, F; Reinhold, A J

    1993-01-01

    Community-based groups are organized around particular aspects of early childhood development (ECD), such as literacy, parent education, and early childhood activities. In the Colombian national program, community households call upon women to devote a portion of their home to organized child care for minimal material reward. The Indian Child Development Service subsidizes the payment of organizers; and Kenyan parents construct basic preschool facilities, provide school lunches, and subsidize a teacher. In such cases the government plays a subordinate role, while the burden of program maintenance is carried by the community. These programs share the characteristics that children and adults learn side by side; adult learning ranges from women's literacy, to health, organizational issues, or small-scale economic development; a strong cultural component emphasizes mother tongue language learning, indigenous child-rearing practices, and local working models; physical structures are in homes; capacity-building for the adults is central which will be transferred to other spheres of community life. In the remote coastal villages of Colombia, an organization called Promesa works with mothers on designing their preschool children's educational activities. Promesa began to confront other priority needs in the villages, especially in environmental health and malaria control. A 1990 assessment related that participants' pride, self-confidence, and ability to solve problems regarding the healthy development of their children increased; groups learned to make use of the physical, human, and institutional resources from their environments; and participants' children remained in school and performed better. Conclusions from a decade of loose experimentation suggest that through communication community women can be organized to provide basic early education and early childhood activities can help rural children over the cultural barrier of school.

  4. Origin and dynamic lineage characteristics of the developing Drosophila midgut stem cells.

    Science.gov (United States)

    Takashima, Shigeo; Aghajanian, Patrick; Younossi-Hartenstein, Amelia; Hartenstein, Volker

    2016-08-15

    Proliferating intestinal stem cells (ISCs) generate all cell types of the Drosophila midgut, including enterocytes, endocrine cells, and gland cells (e.g., copper cells), throughout the lifetime of the animal. Among the signaling mechanisms controlling the balance between ISC self-renewal and the production of different cell types, Notch (N) plays a pivotal role. In this paper we investigated the emergence of ISCs during metamorphosis and the role of N in this process. Precursors of the Drosophila adult intestinal stem cells (pISCs) can be first detected within the pupal midgut during the first hours after onset of metamorphosis as motile mesenchymal cells. pISCs perform 2-3 rounds of parasynchronous divisions. The first mitosis yields only an increase in pISC number. During the following rounds of mitosis, dividing pISCs give rise to more pISCs, as well as the endocrine cells that populate the midgut of the eclosing fly. Enterocytes do not appear among the pISC progeny until around the time of eclosion. The "proendocrine" gene prospero (pros), expressed from mid-pupal stages onward in pISCs, is responsible to advance the endocrine fate in these cells; following removal of pros, pISCs continue to proliferate, but endocrine cells do not form. Conversely, the onset of N activity that occurs around the stage when pros comes on restricts pros expression among pISCs. Loss of N abrogates proliferation and switches on an endocrine fate among all pISCs. Our results suggest that a switch depending on the activity of N and pros acts at the level of the pISC to decide between continued proliferation and endocrine differentiation.

  5. Alternative pre-mRNA splicing in Drosophila spliceosomal assembly factor RNP-4F during development.

    Science.gov (United States)

    Fetherson, Rebecca A; Strock, Stephen B; White, Kristen N; Vaughn, Jack C

    2006-04-26

    The 5'- and 3'-UTR regions in pre-mRNAs play a variety of roles in controlling eukaryotic gene expression, including translational modulation. Here we report the results of a systematic study of alternative splicing in rnp-4f, which encodes a Drosophila spliceosomal assembly factor. We show that most of the nine introns are constitutively spliced, but several patterns of alternative splicing are observed in two pre-mRNA regions including the 5'-UTR. Intron V is shown to be of recent evolutionary origin and is infrequently spliced, resulting in generation of an in-frame stop codon and a predicted truncated protein lacking a nuclear localization signal, so that alternative splicing regulates its subcellular localization. Intron 0, located in the 5'-UTR, is subject to three different splicing decisions in D. melanogaster. Northern analysis of poly(A+) mRNAs reveals two differently sized rnp-4f mRNA isoforms in this species. A switch in relative isoform abundance occurs during mid-embryo stages, when the larger isoform becomes more abundant. This isoform is shown to represent intron 0 unspliced mRNA, whereas the smaller transcript represents the product of alternative splicing. Comparative genomic analysis predicts that intron 0 is present in diverse Drosophila species. Intron 0 splicing results in loss of an evolutionarily conserved stem-loop constituting a potential cis-regulatory element at the 3'-splice site. A model is proposed for the role of this element both in 5'-UTR alternative splicing decisions and in RNP-4F translational modulation. Preliminary evidences in support of our model are discussed.

  6. The Early Development of Kinetic Theory.

    Science.gov (United States)

    Whitaker, Robert D.

    1979-01-01

    A review of the work of Bernoulli and other early contributors to kinetic theory. One significant point is that the most outstanding work in this early period was done by a little-known Scotsman, John J. Waterston. (BB)

  7. Receptor-Type Guanylyl Cyclase at 76C (Gyc76C) Regulates De Novo Lumen Formation during Drosophila Tracheal Development

    Science.gov (United States)

    Patel, Unisha

    2016-01-01

    Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena form de novo to connect the different tracheal branches into an interconnected network of tubes. Here, we identify a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C) in de novo lumen formation in the Drosophila trachea. We show that in embryos mutant for gyc76C or its downsteam effector protein kinase G (PKG) 1, tracheal lumena are disconnected. Dorsal trunk (DT) cells of gyc76C mutant embryos migrate to contact each other and complete the initial steps of lumen formation, such as the accumulation of E-cadherin (E-cad) and formation of an actin track at the site of lumen formation. However, the actin track and E-cad contact site of gyc76C mutant embryos did not mature to become a new lumen and DT lumena did not fuse. We also observed failure of the luminal protein Vermiform to be secreted into the site of new lumen formation in gyc76C mutant trachea. These DT lumen formation defects were accompanied by altered localization of the Arf-like 3 GTPase (Arl3), a known regulator of vesicle-vesicle and vesicle-membrane fusion. In addition to the DT lumen defect, lumena of gyc76C mutant terminal cells were shorter compared to wild-type cells. These studies show that Gyc76C and downstream PKG-dependent signaling regulate de novo lumen formation in the tracheal DT and terminal cells, most likely by affecting Arl3-mediated luminal secretion. PMID:27642749

  8. Telomeric trans-silencing in Drosophila melanogaster: tissue specificity, development and functional interactions between non-homologous telomeres.

    Directory of Open Access Journals (Sweden)

    Thibaut Josse

    Full Text Available BACKGROUND: The study of P element repression in Drosophila melanogaster led to the discovery of the telomeric Trans-Silencing Effect (TSE, a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences, "TAS" has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. TSE can show variegation in ovaries, displays a maternal effect as well as an epigenetic transmission through meiosis and involves heterochromatin and RNA silencing pathways. PRINCIPAL FINDINGS: Here, we analyze phenotypic and genetic properties of TSE. We report that TSE does not occur in the soma at the adult stage, but appears restricted to the female germline. It is detectable during development at the third instar larvae where it presents the same tissue specificity and maternal effect as in adults. Transgenes located in TAS at the telomeres of the main chromosomes can be silencers which in each case show the maternal effect. Silencers located at non-homologous telomeres functionally interact since they stimulate each other via the maternally-transmitted component. All germinally-expressed euchromatic transgenes tested, located on all major chromosomes, were found to be repressed by a telomeric silencer: thus we detected no TSE escaper. The presence of the euchromatic target transgene is not necessary to establish the maternal inheritance of TSE, responsible for its epigenetic behavior. A single telomeric silencer locus can simultaneously repress two P-lacZ targets located on different chromosomal arms. CONCLUSIONS AND SIGNIFICANCE: Therefore TSE appears to be a widespread phenomenon which can involve different telomeres and work across the genome. It can explain the P cytotype establishment by telomeric P elements in natural Drosophila populations.

  9. Master regulators in development: Views from the Drosophila retinal determination and mammalian pluripotency gene networks.

    Science.gov (United States)

    Davis, Trevor L; Rebay, Ilaria

    2017-01-15

    Among the mechanisms that steer cells to their correct fate during development, master regulatory networks are unique in their sufficiency to trigger a developmental program outside of its normal context. In this review we discuss the key features that underlie master regulatory potency during normal and ectopic development, focusing on two examples, the retinal determination gene network (RDGN) that directs eye development in the fruit fly and the pluripotency gene network (PGN) that maintains cell fate competency in the early mammalian embryo. In addition to the hierarchical transcriptional activation, extensive positive transcriptional feedback, and cooperative protein-protein interactions that enable master regulators to override competing cellular programs, recent evidence suggests that network topology must also be dynamic, with extensive rewiring of the interactions and feedback loops required to navigate the correct sequence of developmental transitions to reach a final fate. By synthesizing the in vivo evidence provided by the RDGN with the extensive mechanistic insight gleaned from the PGN, we highlight the unique regulatory capabilities that continual reorganization into new hierarchies confers on master control networks. We suggest that deeper understanding of such dynamics should be a priority, as accurate spatiotemporal remodeling of network topology will undoubtedly be essential for successful stem cell based therapeutic efforts.

  10. The development of storytelling in early childhood

    Directory of Open Access Journals (Sweden)

    Ljubica Marjanovič Umek

    2011-01-01

    Full Text Available Storytelling is an important aspect of child's language competence, which largely depends on her/his understanding and expression of a decontextualised content and develops rapidly in the period between the second and sixth year of life. The purpose of this study was to examine age differences in children's storytelling in the period between the third and sixth year of age. In addition, we considered the effect of gender on storytelling of children of different ages. The sample included 156 children aged from 3 to 6 years, who were divided into 3 age groups, namely children, aged 3, 4 and 5 years. Child's storytelling competence was assessed with the Little Glove Storytelling Test. Children's stories told by a standard set of illustrations, were analyzed in terms of criteria, designed to assess the developmental level of the stories. The criteria refer to the words, included in the story, the grammatical structure and the content of the story. The obtained results suggested that several important changes in the development of storytelling occur within the period of early childhood. The 5-years-old children told longer stories with a more complex grammatical structure and a coherent content as the 3-years-old children. Children's achievements on the individual criteria for assessing the developmental level of the stories progressed relatively steadily through all three age groups. The results also showed that gender had no significant effect on the storytelling of children of different ages.

  11. Nutrition and brain development in early life.

    Science.gov (United States)

    Prado, Elizabeth L; Dewey, Kathryn G

    2014-04-01

    Presented here is an overview of the pathway from early nutrient deficiency to long-term brain function, cognition, and productivity, focusing on research from low- and middle-income countries. Animal models have demonstrated the importance of adequate nutrition for the neurodevelopmental processes that occur rapidly during pregnancy and infancy, such as neuron proliferation and myelination. However, several factors influence whether nutrient deficiencies during this period cause permanent cognitive deficits in human populations, including the child's interaction with the environment, the timing and degree of nutrient deficiency, and the possibility of recovery. These factors should be taken into account in the design and interpretation of future research. Certain types of nutritional deficiency clearly impair brain development, including severe acute malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency. While strategies such as salt iodization and micronutrient powders have been shown to improve these conditions, direct evidence of their impact on brain development is scarce. Other strategies also require further research, including supplementation with iron and other micronutrients, essential fatty acids, and fortified food supplements during pregnancy and infancy. © 2014 International Life Sciences Institute.

  12. Effects of dietary folic acid level and symbiotic folate production on fitness and development in the fruit fly Drosophila melanogaster.

    Science.gov (United States)

    Blatch, Sydella A; Meyer, Kyle W; Harrison, Jon F

    2010-01-01

    Folic acid is a vitamin for probably all animals. When converted to folate forms, it is used in DNA synthesis and amino acid metabolism. Literature suggests insects must consume folates, folates do not affect others, is a toxin for some, and that a few insects synthesize it. It has been reported that Drosophila melanogaster does not consistently need dietary folate because it can synthesize it. This seems unlikely since animals generally lack this ability. More likely, folates thought to have been made by the fly came from microbial symbionts. We aimed to clarify how dietary folic acid affects fitness and development in fruit flies and whether flies may receive folates from microbial symbionts. We found larvae were more viable and developed faster with increasing dietary folic acid, with the surprising exception that larvae fed nearly-zero folic acid developed faster. Their body folate levels did not significantly differ from those that consumed up to 600 times more folic acid. However, these flies fed little folate only achieved normal body folate levels and development times when antibiotics were excluded from the diet. When flies consumed near-zero folates with antibiotics, their body folate levels decreased and development was prolonged. An assay for the endosymbiont Wolbachia in flies used to generate the experimental flies did not show presence of these bacteria. Our data suggest D. melanogaster can harbor unknown bacterial symbiont(s) that provide essential folates to their host when it is scarce in the diet, allowing the fruit fly to maintain growth and development.

  13. The wings of Bombyx mori develop from larval discs exhibiting an early differentiated state: a preliminary report

    Indian Academy of Sciences (India)

    Madhuri Kango-Singh; Amit Singh; K P Gopinathan

    2001-06-01

    Lepidopteran insects present a complex organization of appendages which develop by various mechanisms. In the mulberry silkworm, Bombyx mori a pair of meso- and meta-thoracic discs located on either side in the larvae gives rise to the corresponding fore- and hind-wings of the adult. These discs do not experience massive cell rearrangements during metamorphosis and display the adult wing vein pattern. We have analysed wing development in B. mori by two approaches, viz., expression of patterning genes in larval wing discs, and regulatory capacities of larval discs following explantation or perturbation. Expression of Nubbin is seen all over the presumptive wing blade domains unlike in Drosophila, where it is confined to the hinge and the wing pouch. Excision of meso- and meta-thoracic discs during the larval stages resulted in emergence of adult moths lacking the corresponding wings without any loss of thoracic tissues suggesting independent origin of wing and thoracic primordia. The expression of wingless and distal-less along the dorsal/ventral margin in wing discs correlated well with their expression profile in adult Drosophila wings. Partially excised wing discs did not show in situ regeneration or duplication suggesting their early differentiation. The presence of adult wing vein patterns discernible in larval wing discs and the patterns of marker gene expression as well as the inability of these discs to regulate growth suggested that wing differentiation is achieved early in B. mori. The timings of morphogenetic events are different and the wing discs behave like presumptive wing buds opening out as wing blades in B. mori unlike evagination of only the pouch region as wing blades seen in Drosophila.

  14. Sterol requirements in Drosophila melanogaster

    OpenAIRE

    Almeida de Carvalho, Maria Joao

    2009-01-01

    Sterol is an abundant component of eukaryotic cell membranes and is thought to influence membrane properties such as permeability, fluidity and microdomain formation. Drosophila is an excellent model system in which to study functional requirements for membrane sterol because, although it does not synthesize sterol, it nevertheless requires sterols to complete development. Moreover, Drosophila normally incorporates sterols into cell membranes. Thus, dietary sterol depletion can be used to ...

  15. Plasticity of both planar cell polarity and cell identity during the development of Drosophila.

    Science.gov (United States)

    Saavedra, Pedro; Vincent, Jean-Paul; Palacios, Isabel M; Lawrence, Peter A; Casal, José

    2014-02-11

    Drosophila has helped us understand the genetic mechanisms of pattern formation. Particularly useful have been those organs in which different cell identities and polarities are displayed cell by cell in the cuticle and epidermis (Lawrence, 1992; Bejsovec and Wieschaus, 1993; Freeman, 1997). Here we use the pattern of larval denticles and muscle attachments and ask how this pattern is maintained and renewed over the larval moult cycles. During larval growth each epidermal cell increases manyfold in size but neither divides nor dies. We follow individuals from moult to moult, tracking marked cells and find that, as cells are repositioned and alter their neighbours, their identities change to compensate and the pattern is conserved. Single cells adopting a new fate may even acquire a new polarity: an identified cell that makes a forward-pointing denticle in the first larval stage may make a backward-pointing denticle in the second and third larval stages. DOI: http://dx.doi.org/10.7554/eLife.01569.001.

  16. The Development Of Drosophila Melanogaster under Different Duration Space Flight and Subsequent Adaptation to Earth Gravity.

    Science.gov (United States)

    Ogneva, Irina V; Belyakin, Stepan N; Sarantseva, Svetlana V

    2016-01-01

    In prospective human exploration of outer space, the need to preserve a species over several generations under changed gravity conditions may arise. This paper demonstrates our results in the creation of the third generation of fruit fly Drosophila melanogaster (third-stage larvae) during the 44.5-day space flight (Foton-M4 satellite (2014, Russia)), then the fourth generation on Earth and the fifth generation again in conditions of the 12-day space flight (2014, in the Russian Segment of the ISS). The species preserves fertility despite a number of changes in the level of expression and content of cytoskeletal proteins, which are the key components of the cleavage spindle and the contractile ring of cells. The results of transcriptome screening and space analysis of cytoskeletal proteins show that the exposure to weightless conditions leads to the increased transcription of metabolic genes, cuticle components and the decreased transcription of genes involved in morphogenesis, cell differentiation, cytoskeletal organization and genes associated with the plasma membrane. "Subsequent" exposure to the microgravity for 12 days resulted in an even more significant increase/decrease in the transcription of the same genes. On the contrary, the transition from the microgravity conditions to the gravity of Earth leads to the increased transcription of genes whose products are involved in the morphogenesis, cytoskeletal organization, motility of cells and transcription regulation, and to the decreased transcription of cuticle genes and proteolytic processes.

  17. R7 Photoreceptor Specification in the Developing Drosophila Eye: The Role of the Transcription Factor Deadpan.

    Directory of Open Access Journals (Sweden)

    Yannis Emmanuel Mavromatakis

    2016-07-01

    Full Text Available As cells proceed along their developmental pathways they make a series of sequential cell fate decisions. Each of those decisions needs to be made in a robust manner so there is no ambiguity in the state of the cell as it proceeds to the next stage. Here we examine the decision made by the Drosophila R7 precursor cell to become a photoreceptor and ask how the robustness of that decision is achieved. The transcription factor Tramtrack (Ttk inhibits photoreceptor assignment, and previous studies found that the RTK-induced degradation of Ttk was critically required for R7 specification. Here we find that the transcription factor Deadpan (Dpn is also required; it is needed to silence ttk transcription, and only when Ttk protein degradation and transcriptional silencing occur together is the photoreceptor fate robustly achieved. Dpn expression needs to be tightly restricted to R7 precursors, and we describe the role played by Ttk in repressing dpn transcription. Thus, Dpn and Ttk act as mutually repressive transcription factors, with Dpn acting to ensure that Ttk is effectively removed from R7, and Ttk acting to prevent Dpn expression in other cells. Furthermore, we find that N activity is required to promote dpn transcription, and only in R7 precursors does the removal of Ttk coincide with high N activity, and only in this cell does Dpn expression result.

  18. Spectrin tetramer formation is not required for viable development in Drosophila.

    Science.gov (United States)

    Khanna, Mansi R; Mattie, Floyd J; Browder, Kristen C; Radyk, Megan D; Crilly, Stephanie E; Bakerink, Katelyn J; Harper, Sandra L; Speicher, David W; Thomas, Graham H

    2015-01-01

    The dominant paradigm for spectrin function is that (αβ)2-spectrin tetramers or higher order oligomers form membrane-associated two-dimensional networks in association with F-actin to reinforce the plasma membrane. Tetramerization is an essential event in such structures. We characterize the tetramerization interaction between α-spectrin and β-spectrins in Drosophila. Wild-type α-spectrin binds to both β- and βH-chains with high affinity, resembling other non-erythroid spectrins. However, α-spec(R22S), a tetramerization site mutant homologous to the pathological α-spec(R28S) allele in humans, eliminates detectable binding to β-spectrin and reduces binding to βH-spectrin ∼1000-fold. Even though spectrins are essential proteins, α-spectrin(R22S) rescues α-spectrin mutants to adulthood with only minor phenotypes indicating that tetramerization, and thus conventional network formation, is not the essential function of non-erythroid spectrin. Our data provide the first rigorous test for the general requirement for tetramer-based non-erythroid spectrin networks throughout an organism and find that they have very limited roles, in direct contrast to the current paradigm.

  19. Early gene Broad complex plays a key role in regulating the immune response triggered by ecdysone in the Malpighian tubules of Drosophila melanogaster.

    Science.gov (United States)

    Verma, Puja; Tapadia, Madhu G

    2015-08-01

    In insects, humoral response to injury is accomplished by the production of antimicrobial peptides (AMPs) which are secreted in the hemolymph to eliminate the pathogen. Drosophila Malpighian tubules (MTs), however, are unique immune organs that show constitutive expression of AMPs even in unchallenged conditions and the onset of immune response is developmental stage dependent. Earlier reports have shown ecdysone positively regulates immune response after pathogenic challenge however, a robust response requires prior potentiation by the hormone. Here we provide evidence to show that MTs do not require prior potentiation with ecdysone hormone for expression of AMPs and they respond to ecdysone very fast even without immune challenge, although the different AMPs Diptericin, Cecropin, Attacin, Drosocin show differential expression in response to ecdysone. We show that early gene Broad complex (BR-C) could be regulating the IMD pathway by activating Relish and physically interacting with it to activate AMPs expression. BR-C depletion from Malpighian tubules renders the flies susceptible to infection. We also show that in MTs ecdysone signaling is transduced by EcR-B1 and B2. In the absence of ecdysone signaling the IMD pathway associated genes are down regulated and activation and translocation of transcription factor Relish is also affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.

    Directory of Open Access Journals (Sweden)

    Michael D Blower

    2006-07-01

    Full Text Available The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC, which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization.

  1. Early Parental Depression and Child Language Development

    Science.gov (United States)

    Paulson, James F.; Keefe, Heather A.; Leiferman, Jenn A.

    2009-01-01

    Objective: To examine the effects of early maternal and paternal depression on child expressive language at age 24 months and the role that parent-to-child reading may play in this pathway. Participants and methods: The 9-month and 24-month waves from a national prospective study of children and their families, the Early Childhood Longitudinal…

  2. A stochastic model for early placental development.

    KAUST Repository

    Cotter, Simon L

    2014-08-01

    In the human, placental structure is closely related to placental function and consequent pregnancy outcome. Studies have noted abnormal placental shape in small-for-gestational-age infants which extends to increased lifetime risk of cardiovascular disease. The origins and determinants of placental shape are incompletely understood and are difficult to study in vivo. In this paper, we model the early development of the human placenta, based on the hypothesis that this is driven by a chemoattractant effect emanating from proximal spiral arteries in the decidua. We derive and explore a two-dimensional stochastic model, and investigate the effects of loss of spiral arteries in regions near to the cord insertion on the shape of the placenta. This model demonstrates that disruption of spiral arteries can exert profound effects on placental shape, particularly if this is close to the cord insertion. Thus, placental shape reflects the underlying maternal vascular bed. Abnormal placental shape may reflect an abnormal uterine environment, predisposing to pregnancy complications. Through statistical analysis of model placentas, we are able to characterize the probability that a given placenta grew in a disrupted environment, and even able to distinguish between different disruptions.

  3. Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis

    OpenAIRE

    Spracklen, Andrew J.; Kelpsch, Daniel J.; Chen, Xiang; Spracklen, Cassandra N.; Tootle, Tina L.

    2014-01-01

    Prostaglandins (PGs)—lipid signals produced downstream of cyclooxygenase (COX) enzymes—regulate actin dynamics in cell culture and platelets, but their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton—temporal restriction of actin remodeling during oogenesis. PGs are required for actin filament bundle formation during stage 10B (S10B). In addition, loss of Pxt results in extensive early actin ...

  4. Transcriptional Activation of the Zygotic Genome in Drosophila.

    Science.gov (United States)

    Harrison, Melissa M; Eisen, Michael B

    2015-01-01

    During the first stages of metazoan development, the genomes of the highly specified sperm and egg must unite and be reprogrammed to allow for the generation of a new organism. This process is controlled by maternally deposited products. Initially, the zygotic genome is largely transcriptionally quiescent, and it is not until hours later that the zygotic genome takes control of development. The transcriptional activation of the zygotic genome is tightly coordinated with the degradation of the maternal products. Here, we review the current understanding of the processes that mediate the reprogramming of the early embryonic genome and facilitate transcriptional activation during the early stages of Drosophila development.

  5. armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila.

    Science.gov (United States)

    Müller, H A; Wieschaus, E

    1996-07-01

    Cellularization of the Drosophila embryo results in the formation of a cell monolayer with many characteristics of a polarized epithelium. We have used antibodies specific to cellular junctions and nascent plasma membranes to study the formation of the zonula adherens (ZA) in relation to the establishment of basolateral membrane polarity. The same approach was then used as a test system to identify X-linked zygotically active genes required for ZA formation. We show that ZA formation begins during cellularization and that the basolateral membrane domain is established at mid-gastrulation. By creating deficiencies for defined regions of the X chromosome, we have identified genes that are required for the formation of the ZA and the generation of basolateral membrane polarity. We show that embryos mutant for both stardust (sdt) and bazooka (baz) fail to form a ZA. In addition to the failure to establish the ZA, the formation of the monolayered epithelium is disrupted after cellularization, resulting in formation of a multilayered cell sheet by mid-gastrulation. SEM analysis of mutant embryos revealed a conversion of cells exhibiting epithelial characteristics into cells exhibiting mesenchymal characteristics. To investigate how mutations that affect an integral component of the ZA itself influence ZA formation, we examined embryos with reduced maternal and zygotic supply of wild-type Arm protein. These embryos, like embryos mutant for both sdt and baz, exhibit an early disruption of ZA formation. These results suggest that early stages in the assembly of the ZA are critical for the stability of the polarized blastoderm epithelium.

  6. The Combined Effect of Methyl- and Ethyl-Paraben on Lifespan and Preadult Development Period of Drosophila melanogaster (Diptera: Drosophilidae).

    Science.gov (United States)

    Chen, Qi; Pan, Chenguang; Li, Yajuan; Zhang, Min; Gu, Wei

    2016-01-01

    Parabens are widely used as preservative substances in foods, pharmaceuticals, industrial products, and cosmetics. But several studies have cautioned that parabens have estrogenic or endocrine-disrupting properties. Drosophila melanogaster is an ideal model in vivo to detect the toxic effects of chemistry. The study was designed to assess the potential additive toxic effects of methylparaben (MP) and ethylparaben (EP) mixture (MP + EP) on lifespan and preadult development period in D. melanogaster The data revealed that the MP + EP can reduce the longevity of flies compared with the control group, consistent with a significant reduction in malondialdehyde levels and an increase in superoxide dismutase activities. Furthermore, MP + EP may have a greater toxic effect on longevity of flies than separate using with the same concentration. Additionally, parabens had a nonmonotonic dose-response effect on D. melanogaster preadult development period, showing that MP + EP delayed preadult development period compared with control group while individual MP or EP significantly shortened (P melanogaster. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

  7. Mapping Gene Regulatory Networks in Drosophila Eye Development by Large-Scale Transcriptome Perturbations and Motif Inference

    Directory of Open Access Journals (Sweden)

    Delphine Potier

    2014-12-01

    Full Text Available Genome control is operated by transcription factors (TFs controlling their target genes by binding to promoters and enhancers. Conceptually, the interactions between TFs, their binding sites, and their functional targets are represented by gene regulatory networks (GRNs. Deciphering in vivo GRNs underlying organ development in an unbiased genome-wide setting involves identifying both functional TF-gene interactions and physical TF-DNA interactions. To reverse engineer the GRNs of eye development in Drosophila, we performed RNA-seq across 72 genetic perturbations and sorted cell types and inferred a coexpression network. Next, we derived direct TF-DNA interactions using computational motif inference, ultimately connecting 241 TFs to 5,632 direct target genes through 24,926 enhancers. Using this network, we found network motifs, cis-regulatory codes, and regulators of eye development. We validate the predicted target regions of Grainyhead by ChIP-seq and identify this factor as a general cofactor in the eye network, being bound to thousands of nucleosome-free regions.

  8. E2F and p53 induce apoptosis independently during Drosophila development but intersect in the context of DNA damage.

    Directory of Open Access Journals (Sweden)

    Nam-Sung Moon

    2008-08-01

    Full Text Available In mammalian cells, RB/E2F and p53 are intimately connected, and crosstalk between these pathways is critical for the induction of cell cycle arrest or cell death in response to cellular stresses. Here we have investigated the genetic interactions between RBF/E2F and p53 pathways during Drosophila development. Unexpectedly, we find that the pro-apoptotic activities of E2F and p53 are independent of one another when examined in the context of Drosophila development: apoptosis induced by the deregulation of dE2F1, or by the overexpression of dE2F1, is unaffected by the elimination of dp53; conversely, dp53-induced phenotypes are unaffected by the elimination of dE2F activity. However, dE2F and dp53 converge in the context of a DNA damage response. Both dE2F1/dDP and dp53 are required for DNA damage-induced cell death, and the analysis of rbf1 mutant eye discs indicates that dE2F1/dDP and dp53 cooperatively promote cell death in irradiated discs. In this context, the further deregulation in the expression of pro-apoptotic genes generates an additional sensitivity to apoptosis that requires both dE2F/dDP and dp53 activity. This sensitivity differs from DNA damage-induced apoptosis in wild-type discs (and from dE2F/dDP-induced apoptosis in un-irradiated rbf1 mutant eye discs by being dependent on both hid and reaper. These results show that pro-apoptotic activities of dE2F1 and dp53 are surprisingly separable: dp53 is required for dE2F-dependent apoptosis in the response to DNA damage, but it is not required for dE2F-dependent apoptosis caused simply by the inactivation of rbf1.

  9. Effects of parasitism by Asobara tabida (Hymenoptera: Braconidae) on the development, survival and activity of Drosophila melanogaster larvae.

    Science.gov (United States)

    Moreau, S J.M.; Dingremont, A; Doury, G; Giordanengo, P

    2002-03-01

    The impact of parasitism by Asobara tabida on Drosophila melanogaster larval development, survival features and larval activity has been investigated using two strains of the parasitoid. The successful parasitism rate of the A1 strain was four times greater than that of the WOPV strain. Both strains induced equivalent mortality rates but hosts parasitized by A1 predominantly died as pupae. The time necessary for the host pupariation and emergence, and the larval weight at 72, 96 and 120 h post-parasitization were measured. Parasitized larvae exhibited longer periods of development and lower weights than controls, especially when parasitized by A1. These results suggest that hosts underwent physiological costs varying with respect to the outcome of the parasitic relationship. Of the parasitoid factors possibly responsible for these costs, we examined venoms for their impact on host mortality. Artificial injections of WOPV venoms induced higher mortality rates than did A1 venoms. Venoms were also found responsible for the induction of a transient paralysis, naturally occuring after parasitization. Again, the strongest effect was observed after parasitization by WOPV or injections of its venoms. This study gives new insights into the intriguing features of A. tabida and constitutes the first report of the paralysing properties of the venoms.

  10. Solanum tuberosum and Lycopersicon esculentum Leaf Extracts and Single Metabolites Affect Development and Reproduction of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Emanuela Ventrella

    Full Text Available Glycoalkaloids are secondary metabolites commonly found in Solanaceae plants. They have anti-bacterial, anti-fungal and insecticidal activities. In the present study we examine the effects of potato and tomato leaf extracts and their main components, the glycoalkaloids α-solanine, α-chaconine and α-tomatine, on development and reproduction of Drosophila melanogaster wild-type flies at different stages. Parental generation was exposed to five different concentrations of tested substances. The effects were examined also on the next, non-exposed generation. In the first (exposed generation, addition of each extract reduced the number of organisms reaching the pupal and imaginal stages. Parent insects exposed to extracts and metabolites individually applied showed faster development. However, the effect was weaker in case of single metabolites than in case of exposure to extracts. An increase of developmental rate was also observed in the next, non-exposed generation. The imagoes of both generations exposed to extracts and pure metabolites showed some anomalies in body size and malformations, such as deformed wings and abdomens, smaller black abdominal zone. Our results further support the current idea that Solanaceae can be an impressive source of molecules, which could efficaciously be used in crop protection, as natural extract or in formulation of single pure metabolites in sustainable agriculture.

  11. Solanum tuberosum and Lycopersicon esculentum Leaf Extracts and Single Metabolites Affect Development and Reproduction of Drosophila melanogaster

    Science.gov (United States)

    Ventrella, Emanuela; Adamski, Zbigniew; Chudzińska, Ewa; Miądowicz-Kobielska, Mariola; Marciniak, Paweł; Büyükgüzel, Ender; Büyükgüzel, Kemal; Erdem, Meltem; Falabella, Patrizia; Scrano, Laura; Bufo, Sabino Aurelio

    2016-01-01

    Glycoalkaloids are secondary metabolites commonly found in Solanaceae plants. They have anti-bacterial, anti-fungal and insecticidal activities. In the present study we examine the effects of potato and tomato leaf extracts and their main components, the glycoalkaloids α-solanine, α-chaconine and α-tomatine, on development and reproduction of Drosophila melanogaster wild-type flies at different stages. Parental generation was exposed to five different concentrations of tested substances. The effects were examined also on the next, non-exposed generation. In the first (exposed) generation, addition of each extract reduced the number of organisms reaching the pupal and imaginal stages. Parent insects exposed to extracts and metabolites individually applied showed faster development. However, the effect was weaker in case of single metabolites than in case of exposure to extracts. An increase of developmental rate was also observed in the next, non-exposed generation. The imagoes of both generations exposed to extracts and pure metabolites showed some anomalies in body size and malformations, such as deformed wings and abdomens, smaller black abdominal zone. Our results further support the current idea that Solanaceae can be an impressive source of molecules, which could efficaciously be used in crop protection, as natural extract or in formulation of single pure metabolites in sustainable agriculture. PMID:27213896

  12. Microgravity effects on Drosophila melanogaster development and aging: comparative analysis of the results of the Fly experiment in the Biokosmos 9 biosatellite flight.

    Science.gov (United States)

    Marco, R; González-Jurado, J; Calleja, M; Garesse, R; Maroto, M; Ramírez, E; Holgado, M C; de Juan, E; Miquel, J

    1992-01-01

    The results are presented of the exposure of Drosophila melanogaster to microgravity conditions during a 15-day biosatellite flight, Biokosmos 9, in a joint ESA-URSS project. The experimental containers were loaded before launch with a set of Drosophila melanogaster Oregon R larvae so that imagoes were due to emerge half-way through the flight. A large number of normally developed larvae were recovered from the space-flown containers. These larvae were able to develop into normal adults confirming earlier results that Drosophila melanogaster of a wild-type constitution can develop normally in the absence of gravity. However, microgravity exposure clearly enhances the number of growing embryos laid by the flies and possibly slows down the developmental pace of the microgravity-exposed animals. Due to some problems in the experimental set-up, this slowing down needs to be verified in future experiments. No live adult that had been exposed to microgravity was recovered from the experiment, so that no life span studies could be carried out, but adult males emerged from the recovered embyros showed a slight shortening in life span and a lower performance in other experimental tests of aging. This agrees with the results of previous experiments performed by our groups.

  13. Classroom Effects of an Early Childhood Educator Professional Development Partnership

    Science.gov (United States)

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly

    2011-01-01

    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  14. Parents' Role in the Early Head Start Children's Language Development

    Science.gov (United States)

    Griswold, Cecelia Smalls

    2014-01-01

    The development of language during a child's early years has been linked to parental involvement. While Early Head Start (EHS) researchers have theorized that parental involvement is an important factor in language development, there has been little research on how parents view their roles in the language development process. The purpose of this…

  15. Classroom Effects of an Early Childhood Educator Professional Development Partnership

    Science.gov (United States)

    Algozzine, Bob; Babb, Julie; Algozzine, Kate; Mraz, Maryann; Kissel, Brian; Spano, Sedra; Foxworth, Kimberly

    2011-01-01

    We evaluated an Early Childhood Educator Professional Development (ECEPD) project that provided high-quality, sustained, and intensive professional development designed to support developmentally appropriate instruction for preschool-age children based on the best available research on early childhood pedagogy, child development, and preschool…

  16. Tsp66E, the Drosophila KAI1 homologue, and Tsp74F function to regulate ovarian follicle cell and wing development by stabilizing integrin localization.

    Science.gov (United States)

    Han, Seung Yeop; Lee, Minjung; Hong, Yoon Ki; Hwang, Soojin; Choi, Gahee; Suh, Yoon Seok; Park, Seung Hwan; Lee, Soojin; Lee, Sang-Hee; Chung, Jongkyeong; Baek, Sung Hee; Cho, Kyoung Sang

    2012-11-16

    The metastasis suppressor KAI1/CD82 has been implicated in various cellular processes; however, its function in development is not fully understood. Here, we generated and characterized mutants of Tsp66E and Tsp74F, which are Drosophila homologues of KAI1/CD82 and Tspan11, respectively. These mutants exhibited egg elongation defects along with disturbed integrin localization and actin polarity. Moreover, the defects were enhanced by mutation of inflated, an αPS2 integrin gene. Mutant ovaries had elevated αPS2 integrin levels and reduced endocytic trafficking. These results suggest that Drosophila KAI1/CD82 affects the polarized localization and the level of integrin, which may contribute to epithelial cell polarity.

  17. Ubiquitous overexpression of a transgene encoding the extracellular portion of the Drosophila Roughest-Irregular Chiasm C protein induces early embryonic lethality

    Directory of Open Access Journals (Sweden)

    LIVIA MODA

    2000-09-01

    Full Text Available The cell adhesion molecule Rst-irreC is a transmembrane glycoprotein of the immunoglobulin superfamily involved in several important developmental processes in Drosophila, including axonal pathfinding in the optic lobe and programmed cell death and pigment cell differentiation in the pupal retina. As an initial step towards the "in vivo'' functional analysis of this protein we have generated transgenic fly stocks carrying a truncated cDNA construct encoding only the extracellular domain of Rst-IrreC under the transcriptional control of the heat shock inducible promoter hsp70. We show that heat-shocking embryos bearing the transgene during the first 8hs of development lead to a 3-4 fold reduction in their viability compared to wild type controls. The embryonic lethality can already be produced by applying the heat pulse in the first 3hs of embryonic development, does not seem to be suppressed in the absence of wildtype product and is progressively reduced as the heat treatment is applied later in embryogenesis. These results are compatible with the hypothesis of the lethal phenotype being primarily due to heterophilic interactions between Rst-IrreC extracellular domain and an yet unknown ligand.

  18. The Formin DAAM Functions as Molecular Effector of the Planar Cell Polarity Pathway during Axonal Development in Drosophila.

    Science.gov (United States)

    Gombos, Rita; Migh, Ede; Antal, Otilia; Mukherjee, Anindita; Jenny, Andreas; Mihály, József

    2015-07-15

    Recent studies established that the planar cell polarity (PCP) pathway is critical for various aspects of nervous system development and function, including axonal guidance. Although it seems clear that PCP signaling regulates actin dynamics, the mechanisms through which this occurs remain elusive. Here, we establish a functional link between the PCP system and one specific actin regulator, the formin DAAM, which has previously been shown to be required for embryonic axonal morphogenesis and filopodia formation in the growth cone. We show that dDAAM also plays a pivotal role during axonal growth and guidance in the adult Drosophila mushroom body, a brain center for learning and memory. By using a combination of genetic and biochemical assays, we demonstrate that Wnt5 and the PCP signaling proteins Frizzled, Strabismus, and Dishevelled act in concert with the small GTPase Rac1 to activate the actin assembly functions of dDAAM essential for correct targeting of mushroom body axons. Collectively, these data suggest that dDAAM is used as a major molecular effector of the PCP guidance pathway. By uncovering a signaling system from the Wnt5 guidance cue to an actin assembly factor, we propose that the Wnt5/PCP navigation system is linked by dDAAM to the regulation of the growth cone actin cytoskeleton, and thereby growth cone behavior, in a direct way.

  19. Lateral gene expression in Drosophila early embryos is supported by Grainyhead-mediated activation and tiers of dorsally-localized repression.

    Directory of Open Access Journals (Sweden)

    Mayra Garcia

    Full Text Available The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind, a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence ("the A-box" present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh, a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator and Cic (repressor may also support a "switch-like" response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo.

  20. Lateral gene expression in Drosophila early embryos is supported by Grainyhead-mediated activation and tiers of dorsally-localized repression.

    Science.gov (United States)

    Garcia, Mayra; Stathopoulos, Angelike

    2011-01-01

    The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence ("the A-box") present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a "switch-like" response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo.

  1. [THE EFFECT OF DIETARY RESTRICTION DURING DEVELOPMENT OF DROSOPHILA MELANOGASTER ON THE ACTIVITY OF ANTIOXIDANT SYSTEM ENZYMES].

    Science.gov (United States)

    Zabuga, O G; Koliada, A K; Kukharskyy, V M; Bazhynova, A I; Vaiserman, A M

    2015-01-01

    In the previous study we demonstrated that dietary restriction only at the development stage of Drosophila melanogaster may impact the life span of adult flies. It was important that we didn't use qualitative (restriction of proteins or other macro- or microelements) and not a calorie restriction as well, but quantitative dietary restriction that was the proportional reduction of all food components in the larval medium. In the situations when the larvae were reared in the medium types, that contained protein and carbohydrate components in concentrations of 90-10% of food components compared to the standard one (100%), the males were characterised with the significant increase in the maximum life span. The average life span was also increased, but only in those male individuals that developed in the medium types, that contained 50% and 60% of food components compared to controls. Such an effect we haven't detected in the female flies. To study the biochemical changes associated with the physiological effects we have determined the activity of the antioxidant enzymes--superoxide dismutase (SOD) and catalase. In the male flies the 50% dietary restriction implemented during the development has led to the significant increase in a SOD and catalase activity. Also the flies of both sexes reared in the medium with the 50% of food components have been characterised with the reduction in the accumulation of glycation end products. According to these results, we suggest that the changes in the activity of antioxidant enzymes may play a role in the increase of the flies life span caused by the dietary restriction during the development.

  2. The developmental transcriptome of Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    University of Connecticut; Graveley, Brenton R.; Brooks, Angela N.; Carlson, Joseph W.; Duff, Michael O.; Landolin, Jane M.; Yang, Li; Artieri, Carlo G.; van Baren, Marijke J.; Boley, Nathan; Booth, Benjamin W.; Brown, James B.; Cherbas, Lucy; Davis, Carrie A.; Dobin, Alex; Li, Renhua; Lin, Wei; Malone, John H.; Mattiuzzo, Nicolas R.; Miller, David; Sturgill, David; Tuch, Brian B.; Zaleski, Chris; Zhang, Dayu; Blanchette, Marco; Dudoit, Sandrine; Eads, Brian; Green, Richard E.; Hammonds, Ann; Jiang, Lichun; Kapranov, Phil; Langton, Laura; Perrimon, Norbert; Sandler, Jeremy E.; Wan, Kenneth H.; Willingham, Aarron; Zhang, Yu; Zou, Yi; Andrews, Justen; Bicke, Peter J.; Brenner, Steven E.; Brent, Michael R.; Cherbas, Peter; Gingeras, Thomas R.; Hoskins, Roger A.; Kaufman, Thomas C.; Oliver, Brian; Celniker, Susan E.

    2010-12-02

    . Whereas, 20% of Drosophila genes are annotated as encoding alternatively spliced premRNAs, splice-junction microarray experiments indicate that this number is at least 40% (ref. 7). Determining the diversity of mRNAs generated by alternative promoters, alternative splicing and RNA editing will substantially increase the inferred protein repertoire. Non-coding RNA genes (ncRNAs) including short interfering RNAs (siRNAs) and microRNAS (miRNAs) (reviewed in ref. 10), and longer ncRNAs such as bxd (ref. 11) and rox (ref. 12), have important roles in gene regulation, whereas others such as small nucleolar RNAs (snoRNAs)and small nuclear RNAs (snRNAs) are important components of macromolecular machines such as the ribosome and spliceosome. The transcription and processing of these ncRNAs must also be fully documented and mapped. As part of the modENCODE project to annotate the functional elements of the D. melanogaster and Caenorhabditis elegans genomes, we used RNA-Seq and tiling microarrays to sample the Drosophila transcriptome at unprecedented depth throughout development from early embryo to ageing male and female adults. We report on a high-resolution view of the discovery, structure and dynamic expression of the D. melanogaster transcriptome.

  3. Dual Language Exposure and Early Bilingual Development

    Science.gov (United States)

    Hoff, Erifka; Core, Cynthia; Place, Silvia; Rumiche, Rosario; Senor, Melissa; Parra, Marisol

    2012-01-01

    The extant literature includes conflicting assertions regarding the influence of bilingualism on the rate of language development. The present study compared the language development of equivalently high-SES samples of bilingually and monolingually developing children from 1 ; 10 to 2 ; 6. The monolingually developing children were significantly…

  4. Dual language exposure and early bilingual development.

    Science.gov (United States)

    Hoff, Erika; Core, Cynthia; Place, Silvia; Rumiche, Rosario; Señor, Melissa; Parra, Marisol

    2012-01-01

    The extant literature includes conflicting assertions regarding the influence of bilingualism on the rate of language development. The present study compared the language development of equivalently high-SES samples of bilingually and monolingually developing children from 1 ; 10 to 2 ; 6. The monolingually developing children were significantly more advanced than the bilingually developing children on measures of both vocabulary and grammar in single language comparisons, but they were comparable on a measure of total vocabulary. Within the bilingually developing sample, all measures of vocabulary and grammar were related to the relative amount of input in that language. Implications for theories of language acquisition and for understanding bilingual development are discussed.

  5. Assessing Home Environment for Early Child Development in Pakistan

    Science.gov (United States)

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum

    2014-01-01

    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  6. Promoting Professional Development for Physical Therapists in Early Intervention

    Science.gov (United States)

    Catalino, Tricia; Chiarello, Lisa A.; Long, Toby; Weaver, Priscilla

    2015-01-01

    Early intervention service providers are expected to form cohesive teams to build the capacity of a family to promote their child's development. Given the differences in personnel preparation across disciplines of service providers, the Early Childhood Personnel Center is creating integrated and comprehensive professional development models for…

  7. Assessing Home Environment for Early Child Development in Pakistan

    Science.gov (United States)

    Nadeem, Sanober; Rafique, Ghazala; Khowaja, Liaquat; Yameen, Anjum

    2014-01-01

    Family environment plays a very important role in early child development and the availability of stimulating material in the early years of a child's life is crucial for optimising development. The Home Observation for Measurement of the Environment (HOME) inventory is one of the most widely used measures to assess the quality and quantity of…

  8. Evaluation of the recombination in somatic cells induced by radiation in different stages of Drosophila larval development; Evaluacion de la recombinacion en celulas somaticas inducida por radiacion en diferentes etapas del desarrollo larvario de Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Cruces, M.P.; Morales R, P. [Instituto nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    The mitotic recombination can happen spontaneously and its frequency is very low, however the recombination rate of a cell can be increased by the exposure to agents which cause damage to DNA. This type of agents are knew commonly as recombinogens. The ionizing radiation and a numerous chemical agents can be mentioned (Vogel, 1992). The objective of this work is to determine if the mutation/recombination rate induced by gamma rays varies with the development stage. In order to realize this investigation it was used the mutation and somatic recombination test of Drosophila wing (Graf and col. 1984). The mwh/ mwh and flr{sup 3}/TM3, Ser stocks were used. (Author)

  9. Development of Entrepreneurship Learning Model for Early Childhood

    Directory of Open Access Journals (Sweden)

    Martha Christianti

    2015-08-01

    Full Text Available This study is an early pace in the research development of entrepreneurship learning model for early childhood. This study aims to explore how learning entrepreneurship that has been done in the early childhood; to know whether parents, teachers, and principals support the entrepreneurship learning; and what kind of values of entrepreneurship can be developed for early childhood. The results of this research are useful to create early childhood entrepreneurial learning design. The research conducts in the form of interviews, observation, and documentation. The result shows that the school which has been developing entrepreneurship has no clear guidance of learning to develop the spirit of entrepreneurship; all teachers and principals in the research agree that entrepreneurship learning developed from an early age. However, there are 90.79% of parents agreed that from an early age has begun to develop the spirit of entrepreneurship and 9.21% said they did not agree; and the values of entrepreneurship that are able to be developed since they are in early age are self-confidence, honesty, independence, responsibility, creative, never give up/hard work, caring for the environment, teamwork, discipline, and respect.

  10. Larval Population Density Alters Adult Sleep in Wild-Type Drosophila melanogaster but Not in Amnesiac Mutant Flies

    OpenAIRE

    Chi, Michael W.; Leslie C. Griffith; Vecsey, Christopher G.

    2014-01-01

    Sleep has many important biological functions, but how sleep is regulated remains poorly understood. In humans, social isolation and other stressors early in life can disrupt adult sleep. In fruit flies housed at different population densities during early adulthood, social enrichment was shown to increase subsequent sleep, but it is unknown if population density during early development can also influence adult sleep. To answer this question, we maintained Drosophila larvae at a range of pop...

  11. Using comparative genomics to develop a molecular diagnosis for the identification of an emerging pest Drosophila suzukii

    Science.gov (United States)

    Drosophilia suzukii (Spotted Wing Drosophila) has recently become a serious invasive pest of fruit crops in the U.S., Canada, and Europe, leading to substantial economic losses. D. suzukii oviposits directly into ripe or ripening fruits making it a direct pest; in contrast, other Drosophilids utili...

  12. School Building in Early Development. Part 1.

    Science.gov (United States)

    Dijkgraaf, C.; Giertz, L. M.

    1975-01-01

    This bulletin, concerned mainly with the educational problems in developing lands, focuses on school development, the future of education, and the schools that will have to be built to meet the needs of the future. The report deals with problems arising from the present rates of dropout in traditional primary education, and proposes possible…

  13. The Early Development of Pharmacology in America.

    Science.gov (United States)

    Parascandola, John

    Presented is a review of the development of the science of pharmacology, the study of the interaction of chemical agents with living matter. The origins of the field are traced from 17th century Europe to the present, with major emphasis upon the scientists and developments made in the field in the United States. (SL)

  14. Early gonad development in zebrafish (Danio rerio)

    African Journals Online (AJOL)

    SAM

    2014-08-13

    Aug 13, 2014 ... months. Many aspects of zebrafish development have been described in the ... development of the nervous system (Kimmel et al., 1994), and aspects of cell ..... to juvenile life stages in the zebrafish (Brown, 1997). Day. 19, therefore .... found throughout the reproductive cycle in fish, but has only been clearly ...

  15. EFECTO DE DENSIDAD POBLACIONAL DE HUEVOS SOBRE VIABILIDAD Y TIEMPO DE DESARROLLO DE Drosophila melanogaster (DROSOPHILIDAE Effect Of Eggs Population Density On Viability And Time Of Development Of Drosophila melanogaster (Drosophilidae

    Directory of Open Access Journals (Sweden)

    CRISTIAN FONG

    Full Text Available Para estimar el efecto de la densidad poblacional de huevos sobre la viabilidad huevoadulto de Drosophila melanogaster se realizaron tres tratamientos en frascos con medio de cultivo agar-banano: a densidad de 10, 50 y 90 huevos. La variable de respuesta fue la proporción de individuos adultos emergidos desde la aparición del primer imago hasta 15 días después de la siembra. Las viabilidades huevo-adulto promedio fueron 0,320, 0,338 y 0,328 para las densidades de 10, 50 y 90 huevos respectivamente. No se evidenciaron diferencias significativas entre los tres tratamientos (p>0.05. Por lo tanto, no se detectó en este estudio influencia de la densidad poblacional de huevos sobre la viabilidad huevo-adulto. Probablemente debido a que la proporción entre el número de huevos y la cantidad de medio fue suficientemente alta para no generar competencia en otros estadios del desarrollo huevo/adulto.For estimating the effect from population density of eggs over viability egg-adult in Drosophila melanogaster, it was made three treatments in flasks with agar-banana culture media: densities of 10, 50 and 90 eggs. The effect evaluated was the adult’s proportion that emerged after 15 days of planting. The mean proportions of viability egg-adult were 0.32, 0.338 and 0.328 for the density of 10, 50 and 90 eggs respectively. Significant differences in viability were not evident (p>0.05. Consequently, it was not found effects from the eggs densities in the present study over egg-adult viability. These results probably were due to that the relation among number of eggs and quantity of culture media was not enough of a high for generate competition at another stadiums through the egg-adult development.

  16. Early development of fern gametophytes in microgravity

    Science.gov (United States)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    2003-01-01

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from 1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in micro-g compared to those developing on earth. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

  17. Early development of fern gametophytes in microgravity

    Science.gov (United States)

    Roux, Stanley J.; Chatterjee, Ani; Hillier, Sheila; Cannon, Tom

    Dormant spores of the fern Ceratopteris richardii were flown on Shuttle mission STS-93 to evaluate the effects of /micro-g on their development and on their pattern of gene expression. Prior to flight the spores were sterilized and sown into one of two environments: (1) Microscope slides in a video-microscopy module; and (2) Petri dishes. All spores were then stored in darkness until use. Spore germination was initiated on orbit after exposure to light. For the spores on microscope slides, cell level changes were recorded through the clear spore coat of the spores by video microscopy. After their exposure to light, spores in petri dishes were frozen in orbit at four different time points during which on earth gravity fixes the polarity of their development. Spores were then stored frozen in Biological Research in Canister units until recovery on earth. The RNAs from these cells and from /1-g control cells were extracted and analyzed on earth after flight to assay changes in gene expression. Video microscopy results revealed that the germinated spores developed normally in microgravity, although the polarity of their development, which is guided by gravity on earth, was random in space. Differential Display-PCR analyses of RNA extracted from space-flown cells showed that there was about a 5% change in the pattern of gene expression between cells developing in /micro-g compared to those developing on earth.

  18. Fruit flies on the front line: the translational impact of Drosophila

    Directory of Open Access Journals (Sweden)

    Norbert Perrimon

    2016-03-01

    Full Text Available Drosophila melanogaster has been adopted as one of the most-used model systems since it was first introduced by Thomas Morgan for the study of heredity in the early 20th century. Its experimental tractability and similarity of its biological pathways to those of humans have placed the model at the forefront of research into human development and disease. With the ongoing accumulation of genetic tools and assays, the fly community has at its fingertips the resources to generate diverse Drosophila disease models for the study of genes and pathways involved in a wide range of disorders. In recent years, the fly has also been used successfully for drug screening. In this Editorial, we introduce a Special Collection of reviews, interviews and original research articles that highlight some of the many ways that Drosophila has made, and continues to make, an impact on basic biological insights and translational science.

  19. Early Speech Motor Development: Cognitive and Linguistic Considerations

    Science.gov (United States)

    Nip, Ignatius S. B.; Green, Jordan R.; Marx, David B.

    2009-01-01

    This longitudinal investigation examines developmental changes in orofacial movements occurring during the early stages of communication development. The goals were to identify developmental trends in early speech motor performance and to determine how these trends differ across orofacial behaviors thought to vary in cognitive and linguistic…

  20. Medical students' professional identity development in an early nursing attachment.

    NARCIS (Netherlands)

    Helmich, E.; Derksen, E.; Prevoo, M.; Laan, R.F.J.M.; Bolhuis, S.; Koopmans, R.T.C.M.

    2010-01-01

    OBJECTIVES: The importance of early clinical experience for medical training is well documented. However, to our knowledge there are no studies that assess the influence of very early nursing attachments on the professional development and identity construction of medical students. Working as an ass

  1. Early psychosis workforce development: Core competencies for mental health professionals working in the early psychosis field.

    Science.gov (United States)

    Osman, Helen; Jorm, Anthony F; Killackey, Eoin; Francey, Shona; Mulcahy, Dianne

    2017-08-09

    The aim of this study was to identify the core competencies required of mental health professionals working in the early psychosis field, which could function as an evidence-based tool to support the early psychosis workforce and in turn assist early psychosis service implementation and strengthen early psychosis model fidelity. The Delphi method was used to establish expert consensus on the core competencies. In the first stage, a systematic literature search was conducted to generate competency items. In the second stage, a panel consisting of expert early psychosis clinicians from around the world was formed. Panel members then rated each of the competency items on how essential they are to the clinical practice of all early psychosis clinicians. In total, 1023 pieces of literature including textbooks, journal articles and grey literature were reviewed. A final 542 competency items were identified for inclusion in the questionnaire. A total of 63 early psychosis experts participated in 3 rating rounds. Of the 542 competency items, 242 were endorsed as the required core competencies. There were 29 competency items that were endorsed by 62 or more experts, and these may be considered the foundational competencies for early psychosis practice. The study generated a set of core competencies that provide a common language for early psychosis clinicians across professional disciplines and country of practice, and potentially are a useful professional resource to support early psychosis workforce development and service reform. © 2017 John Wiley & Sons Australia, Ltd.

  2. School Building in Early Development. Part 2.

    Science.gov (United States)

    Dijkgraaf, C.; Giertz, L. M.

    1975-01-01

    Development is characterized by urbanization. New settlements grow either as enlargements of existing ones or as new population concentrations. Three periods may be distinguished in the growth of a settlement: (1) the wild period of first settling, (2) the consolidation period, and (3) the stabilized society. The number of school-aged children per…

  3. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  4. Early Imagining and the Development of Empathy.

    Science.gov (United States)

    Sutherland, Margaret B.

    1985-01-01

    Considers possible links between development of empathy and some children's spontaneous creation of imaginary companions or situations, citing examples of Agatha Christie's "Autobiography." Questions if such activities show ability to "decenter emotionally." Suggests need for better methods of assessing emotional decentering…

  5. Pharmacometrics in early clinical drug development

    NARCIS (Netherlands)

    Keizer, R.J.

    2010-01-01

    Pharmacometrics, the science of quantitative clinical pharmacology, has been recognized as one of the main research fields able to improve efficiency in drug development, and to reduce attrition rates on the route from drug discovery to approval. This field of drug research, which builds heavily on

  6. Developing an Engineering Identity in Early Childhood

    Science.gov (United States)

    Pantoya, Michelle L.; Aguirre-Munoz, Zenaida; Hunt, Emily M.

    2015-01-01

    This project describes a strategy to introduce young children to engineering in a way that develops their engineering identity. The targeted age group is 3-7 year old students because they rarely experience purposeful engineering instruction. The curriculum was designed around an engineering storybook and included interactive academic discussions…

  7. 果蝇Golgin-84在发育中的表达和功能研究%Studies of Drosophila Golgin-84 Expression and Functions in Development

    Institute of Scientific and Technical Information of China (English)

    侯国丽; 林鑫华; 吴一卉; 刁爱坡

    2013-01-01

    The structure of Golgi apparatus is closely related to membrane transport and normal cellular function.It is already known that the cis-Golgi localized Golgin-84 plays an essential role in the maintenance of Golgi structure in mammalian cells.However,the function of Golgin-84 in development remains unclear.To examine the roles of Golgin-84 in development,we generated and purified the polyclonal antibody against Drosophila Golgin-84,and the UAS-golgin-84-V5 over-expression and golgin-84 RNAi transgenic Drosophila lines were generated.We preliminarily analyzed the function ofgolgin-84 in Drosophila melanogaster during wing development.Western blot and immunofluorescence staining showed that the purified antibody can recognize recombinant and endogenous Golgin-84 protein,and the antibody stained Golgin-84 co-localized with Golgi marker protein GM130 in S2 cells.Golgin-84 was ubiquitously expressed during development in Drosophila melanogaster and abundant in testis.Furthermore,inhibition of Golgin-84 expression resulted in wing defects,and wing growth and patterning defects were observed in the Golgin-84 over-expressed Drosophila.In conclusion,we successfully generated the Golgin-84 antibody and transgenic lines in Drosophila,and examined the function of Golgin-84 in wing development.Our results laid the foundation to further study the physiological function and molecular mechanism ofgolgin-84.%高尔基体形态和结构的维持与真核细胞内的物质运输和细胞正常功能密切相关,高尔基体蛋白Golgin-84对维持高尔基体形态发挥了重要作用,但其在发育中的功能尚不清楚.为了研究Golgin-84在果蝇发育中的作用,成功制备并纯化了抗果蝇Golgin-84的多克隆抗体并成功构建了UAS-golgin-84-V5过表达和golgin-84 RNAi转基因果蝇,并对golgin-84在果蝇发育中的作用作了初步分析.蛋白免疫印迹和免疫荧光染色实验表明2制备的Golgin-84抗体能特异性识别重组和内源Golgin-84

  8. Penicillin: its discovery and early development.

    Science.gov (United States)

    Ligon, B Lee

    2004-01-01

    In August 1928, Alexander Fleming returned from a vacation to his usually messy, disordered laboratory. In one of the Petri dishes that had not been touched by the Lysol, he noticed an unusual phenomenon: separate colonies of staphylococci and, near the dish's edge, a colony of mold approximately 20 mm in diameter. The finding proved to be a watershed in the history of medicine. This discovery lay dormant for some time before other researchers took up the challenge to investigate its clinical possibilities. Two investigators at Oxford, Sir Howard Walter Florey and Ernst Boris Chain, brought penicillin's potential for medical use to fruition and, along with Fleming, shared the 1945 Nobel Prize for Medicine. The discovery and development of penicillin represent one of the most important developments in the annals of medical history. This article presents a brief overview of the events that occurred in the progress from discovery to implementation as a therapeutic agent.

  9. Early development of Thyrsitops lepidopoides (Pisces: Gempylidae

    Directory of Open Access Journals (Sweden)

    Sato Gosuke

    1986-01-01

    Full Text Available Thyrsitops lepidopoides larvae were caught with Bongo nets in the upper 200 m of the ocean from the coast of southern Brazil during 1975-1978. Based on a serie of 271 specimens ranging from 2.5 to 24.0 mm body lenght, morphological and osteological development of the larvae and juveniles is described. Small larvae (2.5-12.0 mm NL can be distinguished from all known gempylid larvae by the presence of a distinct melanophore at the base of the dorsal and anal fins. The larvae have well developed dorsal and ventral spines. It is the only gempylid with six preopercular spines and non-serrated dorsal and ventral spines during the larval stage.

  10. Emc, a negative HLH regulator with multiple functions in Drosophila development.

    Science.gov (United States)

    Campuzano, S

    2001-12-20

    Expression and functional analyses of Emc have demonstrated that it is a prototype for a protein required for multiple processes in development. Initially characterized as a negative regulator of sensory organ development, it was later found to regulate many other developmental processes and cell proliferation. Its ability to block the function of bHLH proteins by forming heterodimers, which are ineffective in DNA binding, accounts for the role of Emc in preventing the acquisition of several cell fates which are under the control of bHLH proteins. However, while maintaining this repressive molecular mechanism, emc also appears to act as a positive regulator of differentiation.

  11. Challenges in early clinical development of adjuvanted vaccines.

    Science.gov (United States)

    Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

    2015-06-08

    A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.

  12. Early influences on the development of food preferences

    National Research Council Canada - National Science Library

    Ventura, Alison K; Worobey, John

    2013-01-01

    .... This early experience serves as the foundation for the continuing development of food preferences across the lifespan, and is shaped by the interplay of biological, social, and environmental factors...

  13. Metabolic gene profile in early human fetal heart development

    National Research Council Canada - National Science Library

    Iruretagoyena, J I; Davis, W; Bird, C; Olsen, J; Radue, R; Teo Broman, A; Kendziorski, C; Splinter BonDurant, S; Golos, T; Bird, I; Shah, D

    2014-01-01

    .... In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database...

  14. The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

    Science.gov (United States)

    2008-07-01

    such a rule , and some of them crossed the vein boundary (arrows in Figure 6 point to these clones). In addition to crossing the vein, the mosaic...9A). The retina is the innermost layer of the eye and is derived embryologically from the outgrowth of the developing brain (Martinez-Morales et al

  15. Early bilingualism, language attainment, and brain development.

    Science.gov (United States)

    Berken, Jonathan A; Gracco, Vincent L; Klein, Denise

    2017-04-01

    The brain demonstrates a remarkable capacity to undergo structural and functional change in response to experience throughout the lifespan. Evidence suggests that, in many domains of skill acquisition, the manifestation of this neuroplasticity depends on the age at which learning begins. The fact that most skills are acquired late in childhood or in adulthood has proven to be a limitation in studies aimed at determining the relationship between age of acquisition and brain plasticity. Bilingualism, however, provides an optimal model for discerning differences in how the brain wires when a skill is acquired from birth, when the brain circuitry for language is being constructed, versus later in life, when the pathways subserving the first language are already well developed. This review examines some of the existing knowledge about optimal periods in language development, with particular attention to the attainment of native-like phonology. It focuses on the differences in brain structure and function between simultaneous and sequential bilinguals and the compensatory mechanisms employed when bilingualism is achieved later in life, based on evidence from studies using a variety of neuroimaging modalities, including positron emission tomography (PET), task-based and resting-state functional magnetic resonance imaging (fMRI), and structural MRI. The discussion concludes with the presentation of recent neuroimaging studies that explore the concept of nested optimal periods in language development and the different neural paths to language proficiency taken by simultaneous and sequential bilinguals, with extrapolation to general notions of the relationship between age of acquisition and ultimate skill performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Immunity through early development of coral larvae.

    Science.gov (United States)

    Palmer, C V; Graham, E; Baird, A H

    2012-10-01

    As a determinant of survival, immunity is likely to be significant in enabling coral larvae to disperse and successfully recruit, however, whether reef-building coral larvae have immune defenses is unknown. We investigated the potential presence and variation in immunity in the lecithotrophic larvae of Acropora tenuis through larval development. Enzymes indicative of tyrosinase and laccase-type melanin-synthesis were quantified, and the concentration of three coral fluorescent proteins was measured over six developmental stages; egg, embryo, motile planula, planula post-exposure to crustose coralline algae (CCA; settlement cue), settled, settled post-exposure to Symbiodinium (endosymbiont). Both types of melanin-synthesis pathways and the three fluorescent proteins were present in A. tenuis throughout development. Laccase-type activity and red fluorescence increased following exposure of planula to CCA, whereas tyrosinase-type activity and cyan fluorescence increased following settlement. No change was detected in the measured parameters following exposure to Symbiodinium. This study is the first to document coral larval immune responses and suggests the melanin-synthesis pathways have disparate roles-the laccase-type potentially non-immunological and the tyrosinase-type in cytotoxic defense. Our results indicate that corals have the potential to resist infection from the earliest life history phase. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Novel level of signalling control in the JAK/STAT pathway revealed by in situ visualisation of protein-protein interaction during Drosophila development.

    Science.gov (United States)

    Brown, Stephen; Hu, Nan; Hombría, James Castelli-Gair

    2003-07-01

    It is commonly accepted that activation of most signalling pathways is induced by ligand receptor dimerisation. This belief has been challenged for some vertebrate cytokine receptors of the JAK/STAT pathway. Here we study whether DOME, the Drosophila receptor of the JAK/STAT pathway, can dimerise and if the dimerisation is ligand-dependent. To analyse DOME homo-dimerisation, we have applied a beta-gal complementation technique that allows the detection of protein interactions in situ. This technique has been used previously in cell culture but this is the first time that it has been applied to whole embryos. We show that this technique, which we rename betalue-betalau technique, can be used to detect DOME homo-dimerisation in Drosophila developing embryos. Despite DOME being ubiquitously expressed, dimerisation is developmentally regulated. We investigate the state of DOME dimerisation in the presence or absence of ligand and show that DOME dimerisation is not ligand-induced, indicating that ligand independent cytokine receptor dimerisation is a conserved feature across phyla. We have further analysed the functional significance of ligand-independent receptor dimerisation by comparing the effects of ectopic ligand expression in cells in which the receptor is, or is not, dimerised. We show that ligand expression can only activate STAT downstream targets or affect embryo development in cells in which the receptor is dimerised. These results suggest a model in which ligand-independent dimerisation of the JAK/STAT receptor confers cells with competence to activate the pathway prior to ligand reception. Thus, competence to induce the JAK/STAT signalling pathway in Drosophila can be regulated by controlling receptor dimerisation prior to ligand binding. These results reveal a novel level of JAK/STAT signalling regulation that could also apply to vertebrates.

  18. Transcriptome Profiling Identifies Multiplexin as a Target of SAGA Deubiquitinase Activity in Glia Required for Precise Axon Guidance During Drosophila Visual Development

    Directory of Open Access Journals (Sweden)

    Jingqun Ma

    2016-08-01

    Full Text Available The Spt-Ada-Gcn5 Acetyltransferase (SAGA complex is a transcriptional coactivator with histone acetylase and deubiquitinase activities that plays an important role in visual development and function. In Drosophila melanogaster, four SAGA subunits are required for the deubiquitination of monoubiquitinated histone H2B (ubH2B: Nonstop, Sgf11, E(y2, and Ataxin 7. Mutations that disrupt SAGA deubiquitinase activity cause defects in neuronal connectivity in the developing Drosophila visual system. In addition, mutations in SAGA result in the human progressive visual disorder spinocerebellar ataxia type 7 (SCA7. Glial cells play a crucial role in both the neuronal connectivity defect in nonstop and sgf11 flies, and in the retinal degeneration observed in SCA7 patients. Thus, we sought to identify the gene targets of SAGA deubiquitinase activity in glia in the Drosophila larval central nervous system. To do this, we enriched glia from wild-type, nonstop, and sgf11 larval optic lobes using affinity-purification of KASH-GFP tagged nuclei, and then examined each transcriptome using RNA-seq. Our analysis showed that SAGA deubiquitinase activity is required for proper expression of 16% of actively transcribed genes in glia, especially genes involved in proteasome function, protein folding and axon guidance. We further show that the SAGA deubiquitinase-activated gene Multiplexin (Mp is required in glia for proper photoreceptor axon targeting. Mutations in the human ortholog of Mp, COL18A1, have been identified in a family with a SCA7-like progressive visual disorder, suggesting that defects in the expression of this gene in SCA7 patients could play a role in the retinal degeneration that is unique to this ataxia.

  19. Assessment of early child development: what, why, and how?

    Directory of Open Access Journals (Sweden)

    Tajana Brajović

    2010-05-01

    Full Text Available Motor skills, language, social and personal development as well as cognitive abilities are often the focus of early child development assessment and monitoring. The article presents some of the developmental milestones in these areas of child development. At the same time the article demonstrates that early child development assessment surpasses merely the orientation acording to developmental milestones. As a part of primary health prevention in Slovenia, identification of children with potential developmental delays is performed with the Denver developmental screening test II and the Systematical psychological examination of the three-year-old procedure. The purpose of applying developmental screening tests is early identification of children with developmental problems, as well as preparation of effective early interventions. By applying an appropriate psychological test material, a psychologist is able to assess the type and the stage of child' s psychological problems and delays in different developmental domains. Only psychometrically sound, and standardized tests should be applied in the process of early child development assessment. The work presents some of the practical and theoretical difficulties which practitioners are facing in the process of early child development assessment. Some feasible solutions are provided as well.

  20. doublesex functions early and late in gustatory sense organ development.

    Science.gov (United States)

    Mellert, David J; Robinett, Carmen C; Baker, Bruce S

    2012-01-01

    Somatic sexual dimorphisms outside of the nervous system in Drosophila melanogaster are largely controlled by the male- and female-specific Doublesex transcription factors (DSX(M) and DSX(F), respectively). The DSX proteins must act at the right times and places in development to regulate the diverse array of genes that sculpt male and female characteristics across a variety of tissues. To explore how cellular and developmental contexts integrate with doublesex (dsx) gene function, we focused on the sexually dimorphic number of gustatory sense organs (GSOs) in the foreleg. We show that DSX(M) and DSX(F) promote and repress GSO formation, respectively, and that their relative contribution to this dimorphism varies along the proximodistal axis of the foreleg. Our results suggest that the DSX proteins impact specification of the gustatory sensory organ precursors (SOPs). DSX(F) then acts later in the foreleg to regulate gustatory receptor neuron axon guidance. These results suggest that the foreleg provides a unique opportunity for examining the context-dependent functions of DSX.

  1. Early intestinal growth and development in poultry.

    Science.gov (United States)

    Lilburn, M S; Loeffler, S

    2015-07-01

    While there are many accepted "facts" within the field of poultry science that are in truth still open for discussion, there is little debate with respect to the tremendous genetic progress that has been made with commercial broilers and turkeys (Havenstein et al., 2003, 2007). When one considers the changes in carcass development in poultry meat strains, these genetic "improvements" have not always been accompanied by correlated changes in other physiological systems and this can predispose some birds to developmental anomalies (i.e. ascites; Pavlidis et al., 2007; Wideman et al., 2013). Over the last decade, there has been increased interest in intestinal growth/health as poultry nutritionists have attempted to adopt new approaches to deal with the broader changes in the overall nutrition landscape. This landscape includes not only the aforementioned genetic changes but also a raft of governmental policies that have focused attention on the environment (phosphorus and nitrogen excretion), consumer pressure on the use of antibiotics, and renewable biofuels with its consequent effects on ingredient costs. Intestinal morphology has become a common research tool for assessing nutritional effects on the intestine but it is only one metric among many that can be used and histological results can often be interpreted in a variety of ways. This study will address the broader body of research on intestinal growth and development in commercial poultry and will attempt to integrate the topics of the intestinal: microbial interface and the role of the intestine as an immune tissue under the broad umbrella of intestinal physiology. © 2015 Poultry Science Association Inc.

  2. Rapid and highly accurate detection of Drosophila suzukii, spotted wing Drosophila (Diptera: Drosophilidae) by loop-mediated isothermal amplification assays

    Science.gov (United States)

    Drosophila suzukii, the spotted wing drosophila (SWD), is currently a major pest that causes severe economic losses to thin-skinned, small fruit growers in North America and Europe. The monitoring and early detection of SWD in the field is of the utmost importance for its proper management. Althou...

  3. Molecular basis for the inhibition of Drosophila eye development by Antennapedia.

    Science.gov (United States)

    Plaza, S; Prince, F; Jaeger, J; Kloter, U; Flister, S; Benassayag, C; Cribbs, D; Gehring, W J

    2001-02-15

    Hox genes encoding homeodomain transcriptional regulators are known to specify the body plan of multicellular organisms and are able to induce body plan transformations when misexpressed. These findings led to the hypothesis that duplication events and misexpression of Hox genes during evolution have been necessary for generating the observed morphological diversity found in metazoans. It is known that overexpressing Antennapedia (Antp) in the head induces antenna-to-leg as well as head-to-thorax transformation and eye reduction. At present, little is known about the exact molecular mechanism causing these phenotypes. The aim of this study is to understand the basis of inhibition of eye development. We demonstrate that Antp represses the activity of the eye regulatory cascade. By ectopic expression, we show that Antp antagonizes the activity of the eye selector gene eyeless. Using both in vitro and in vivo experiments, we demonstrate that this inhibitory mechanism involves direct protein-protein interactions between the DNA-binding domains of EY and ANTP, resulting in mutual inhibition.

  4. The yolk syncytial layer in early zebrafish development.

    Science.gov (United States)

    Carvalho, Lara; Heisenberg, Carl-Philipp

    2010-10-01

    The yolk syncytial layer (YSL) plays crucial roles in early zebrafish development. The YSL is a transient extra-embryonic syncytial tissue that forms during early cleavage stages and persists until larval stages. During gastrulation, the YSL undergoes highly dynamic movements, which are tightly coordinated with the movements of the overlying germ layer progenitor cells, and has critical functions in cell fate specification and morphogenesis of the early germ layers. Movement coordination between the YSL and blastoderm cells is dependent on contact between these tissues, and is probably required for the patterning and morphogenetic function of the YSL. In this review, we will discuss recent advances in elucidating the molecular and cellular mechanisms underlying the YSL morphogenesis and movement coordination between the YSL and blastoderm during early development.

  5. Early life origins of psychological development and mental health.

    Science.gov (United States)

    Räikkönen, Katri; Pesonen, Anu-Katriina

    2009-12-01

    According to the Developmental Origins of Health and Disease (DOHaD)-hypothesis, conditions early in life may have life-long consequences. In a series of epidemiological birth cohort and clinical studies and natural experiments, we have had the chance to test the extent to which this hypothesis is useful in understanding individual differences in psychological development and mental health. Our findings have provided evidence that individual differences in cognitive, social and emotional development and in mental health may lie in early life circumstances, and add significantly to the literature by pointing out which periods of early growth are the most critical. These findings are also important in translating pre-clinical evidence to humans. What remains less clear, however, is what the mechanisms of programming are. Thus, further research is needed to elucidate these mechanisms before information on the early life origins of health and disease can be used in designing prevention and intervention programs.

  6. Early Brain and Child Development: Connections to Early Education and Child Care

    Science.gov (United States)

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  7. Integrated and Early Childhood Education: Preparation for Social Development. Theme A: Relevant Provision for Early Childhood.

    Science.gov (United States)

    Axton, J. H. M.

    Factors which influence child development are listed and briefly discussed. These factors are (1) mother's childhood, (2) mother's age, (3) care during pregnancy and delivery, (4) early neonatal factors, (5) birth interval, (6) effect of repeated infection and malnutrition on brain growth and intellectual development, and (7) home environment. The…

  8. Early Brain and Child Development: Connections to Early Education and Child Care

    Science.gov (United States)

    Romano, Judith T.

    2013-01-01

    The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

  9. The Drosophila SRF homolog is expressed in a subset of tracheal cells and maps within a genomic region required for tracheal development.

    Science.gov (United States)

    Affolter, M; Montagne, J; Walldorf, U; Groppe, J; Kloter, U; LaRosa, M; Gehring, W J

    1994-04-01

    The Drosophila homolog of the vertebrate serum response factor (SRF) was isolated by low stringency hybridization. Nucleotide sequence analysis revealed that the Drosophila SRF homolog (DSRF) codes for a protein that displays 93% sequence identity with human SRF in the MADS domain, the region required for DNA binding, dimerization and interaction with accessory factors. The DSRF gene is expressed during several phases of embryonic development. In the egg, both the RNA and the protein are maternal in origin and slowly decrease in amount during gastrulation. After germ band retraction, high levels of zygotic expression are observed in a distinct subset of peripheral tracheal cells distributed throughout the embryo. Many of these cells are at the tip of tracheal branches and are in direct contact with the target tissues. The DSRF gene was mapped to position 60C on the second chromosome, and overlapping deficiencies which remove the gene were identified. Analysis of tracheal development in embryos carrying these deletions revealed a degeneration of most of the major branches of the tracheal system. Although the initial migration of tracheal cells was not affected in those deficient embryos, many tracheal cells appeared not to maintain their correct position and continued to migrate. Thus, the DSRF gene might play a role in the proper formation and maintenance of the trachea.

  10. Understanding Emotional Development: Helping Early Childhood Providers Better Support Families

    Science.gov (United States)

    Edwards, Nicole Megan

    2012-01-01

    This article is intended to provide early childhood providers with a concise overview of emerging emotional development in young children (birth-5), the important role of primary caregivers, and the link between parenting, emotional development, and behavior. Specific suggestions that have been shared with urban Head Start mothers are offered,…

  11. Early Markers of Vulnerable Language Skill Development in Galactosaemia

    Science.gov (United States)

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne

    2014-01-01

    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  12. Early Markers of Vulnerable Language Skill Development in Galactosaemia

    Science.gov (United States)

    Lewis, Fiona M.; Coman, David J.; Syrmis, Maryanne

    2014-01-01

    There are no known biomedical or genetic markers to identify which infants with galactosaemia (GAL) are most at risk of poor language skill development, yet pre-linguistic communicative "red flag" behaviours are recognised as early identifiers of heightened vulnerability to impaired language development. We report on pre-linguistic…

  13. Time Development in the Early History of Social Networks

    DEFF Research Database (Denmark)

    Bruun, Jesper; Bearden, Ian

    2014-01-01

    Studies of the time development of empirical networks usually investigate late stages where lasting connections have already stabilized. Empirical data on early network history are rare but needed for a better understanding of how social network topology develops in real life. Studying students w...

  14. Early Learning and Development: Cultural-Historical Concepts in Play

    Science.gov (United States)

    Fleer, Marilyn

    2010-01-01

    "Early Learning and Development" provides a unique synthesis of cultural-historical theory from Vygotsky, Elkonin and Leontiev in the 20th century to the ground-breaking research of scholars such as Siraj-Blatchford, Kratsova and Hedegaard today. It demonstrates how development and learning are culturally embedded and institutionally defined, and…

  15. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  16. Time Development in the Early History of Social Networks

    DEFF Research Database (Denmark)

    Bruun, Jesper; Bearden, Ian

    2014-01-01

    Studies of the time development of empirical networks usually investigate late stages where lasting connections have already stabilized. Empirical data on early network history are rare but needed for a better understanding of how social network topology develops in real life. Studying students who...... are beginning their studies at a university with no or few prior connections to each other offers a unique opportunity to investigate the formation and early development of link patterns and community structure in social networks. During a nine week introductory physics course, first year physics students were...... asked to identify those with whom they communicated about problem solving in physics during the preceding week. We use these students' self reports to produce time dependent student interaction networks. We investigate these networks to elucidate possible effects of different student attributes in early...

  17. FlyOde - a platform for community curation and interactive visualization of dynamic gene regulatory networks in Drosophila eye development [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stefan A. Koestler

    2015-12-01

    Full Text Available Motivation: Understanding the regulatory mechanisms governing eye development of the model organism Drosophila melanogaster (D. m. requires structured knowledge of the involved genes and proteins, their interactions, and dynamic expression patterns. Especially the latter information is however to a large extent scattered throughout the literature. Results: FlyOde is an online platform for the systematic assembly of data on D. m. eye development. It consists of data on eye development obtained from the literature, and a web interface for users to interactively display these data as a gene regulatory network. Our manual curation process provides high standard structured data, following a specifically designed ontology. Visualization of gene interactions provides an overview of network topology, and filtering according to user-defined expression patterns makes it a versatile tool for daily tasks, as demonstrated by usage examples. Users are encouraged to submit additional data via a simple online form.

  18. On the Morphology of the Drosophila Heart

    Directory of Open Access Journals (Sweden)

    Barbara Rotstein

    2016-04-01

    Full Text Available The circulatory system of Drosophila melanogaster represents an easily amenable genetic model whose analysis at different levels, i.e., from single molecules up to functional anatomy, has provided new insights into general aspects of cardiogenesis, heart physiology and cardiac aging, to name a few examples. In recent years, the Drosophila heart has also attracted the attention of researchers in the field of biomedicine. This development is mainly due to the fact that several genes causing human heart disease are also present in Drosophila, where they play the same or similar roles in heart development, maintenance or physiology as their respective counterparts in humans. This review will attempt to briefly introduce the anatomy of the Drosophila circulatory system and then focus on the different cell types and non-cellular tissue that constitute the heart.

  19. Early feeding practices and development of food allergies.

    Science.gov (United States)

    Lack, Gideon; Penagos, Martin

    2011-01-01

    Despite increasing efforts to prevent food allergies in children, IgE-mediated food allergies continue to rise in westernized countries. Previous preventive strategies such as prolonged exclusive breastfeeding and delayed weaning onto solid foods have more recently been called into question. The present review discusses possible risk factors and theories for the development of food allergy. An alternative hypothesis is proposed, suggesting that early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitization and that early oral exposure of food allergen induces tolerance. Novel interventional strategies to prevent the development of food allergies are also discussed.

  20. The Big Push: Early Development Economics (1945-1975)

    OpenAIRE

    Kartika, Dwintha Maya

    2014-01-01

    This article attempts to analyse the strategies, strengths and weaknesses of early development economics, commonly known as the Big Push era. The article starts with the historical analysis on what could influence the thinking of structuralist approach to development. The next section highlights the common strategies proposed by the development pioneers. This is followed by the assessment of industrialisation strategies based on their strengths and weaknesses of the strategies proposed. Final...

  1. Developing the quality of early childhood mentoring institutions

    Directory of Open Access Journals (Sweden)

    Sri Hartini

    2017-09-01

    Full Text Available The study was to uncover the concept of quality improvement, the supporting and the inhibiting factors within the quality improve and the quality improvement in the early childhood mentoring institutions/kindergarten. The study was a qualitative research. The subjects in the study were kindergarten principals, kindergarten teachers and parents. The data were gathered by means of observation, interview and documentation. For the data analysis, the researcher selected the qualitative descriptive data analysis method. The results of the study were as follows. First, the concept of educational quality improvement in the early childhood mentoring institutions/ kindergarten has been improveed from the vision, the mission and the objectives and the concept includes the aspects of planning, process and output which has synergy from one to another. The planning has been formulated in the curriculum, the syllabus and the daily activity plan. Second, the approach, the strategy and the technique of quality improvement has maximized the well-qualified schools’ resources, have been supported by the sufficient facilities and have been funded by the sufficient budget. Third, the supporting factors within the quality improvement of early childhood mentoring institutions/kindergarten have been the increasing awareness within the society toward the significance of early childhood mentoring institutions, the massive socialization conducted by the Office of Education through the provision of training programs in relation to the early childhood mentoring institution/kindergarten management and the human resources empowerment toward developing the quality of early childhood mentoring institutions. Fourth, the inhibiting factors within the quality improvement of early childhood mentoring institutions have been the lack of society care and participation, the less quality human resources that early childhood mentoring institutions have, the fund limitation, the

  2. Temperament, Executive Control, and ADHD across Early Development

    Science.gov (United States)

    Rabinovitz, Beth B.; O’Neill, Sarah; Rajendran, Khushmand; Halperin, Jeffrey M.

    2015-01-01

    Research examining factors linking early temperament and later ADHD is limited by cross-sectional approaches and having the same informant rate both temperament and psychopathology. We used multi-informant/multi-method longitudinal data to test the hypothesis that negative emotionality during preschool is positively associated with ADHD symptom severity in middle childhood, but developing executive control mediates this relation. Children (N=161) with and without ADHD were evaluated three times: Parent and teacher temperament ratings and NEPSY Visual Attention at ages 3–4 years; WISC-IV Working Memory Index and NEPSY Response Set at age 6 years; and ADHD symptoms using the Kiddie-SADS at age 7 years. Parent and teacher ratings of preschoolers’ temperament were combined to form an Anger/Frustration composite. Similarly, an Executive Functioning composite was derived from age 6 measures. Bootstrapping was used to determine whether age 6 Executive Functioning mediated the relation between early Anger/Frustration and later ADHD symptom severity, while controlling for early executive functioning. Preschoolers’ Anger/Frustration was significantly associated with later ADHD symptoms, with this relation partially mediated by age 6 Executive Functioning. Developing executive control mediates the relation between early Anger/Frustration and later ADHD symptom severity, suggesting that Anger/Frustration influences ADHD symptom severity through its impact on developing executive control. Early interventions targeting the harmful influences of negative emotionality or enhancing executive functioning may diminish later ADHD severity. PMID:26854505

  3. Myoblast fusion in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Haralalka, Shruti [Stowers Institute for Medical Research, Kansas City, MO 64110 (United States); Abmayr, Susan M., E-mail: sma@stowers.org [Stowers Institute for Medical Research, Kansas City, MO 64110 (United States); Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, MO 66160 (United States)

    2010-11-01

    The body wall musculature of a Drosophila larva is composed of an intricate pattern of 30 segmentally repeated muscle fibers in each abdominal hemisegment. Each muscle fiber has unique spatial and behavioral characteristics that include its location, orientation, epidermal attachment, size and pattern of innervation. Many, if not all, of these properties are dictated by founder cells, which determine the muscle pattern and seed the fusion process. Myofibers are then derived from fusion between a specific founder cell and several fusion competent myoblasts (FCMs) fusing with as few as 3-5 FCMs in the small muscles on the most ventral side of the embryo and as many as 30 FCMs in the larger muscles on the dorsal side of the embryo. The focus of the present review is the formation of the larval muscles in the developing embryo, summarizing the major issues and players in this process. We have attempted to emphasize experimentally-validated details of the mechanism of myoblast fusion and distinguish these from the theoretically possible details that have not yet been confirmed experimentally. We also direct the interested reader to other recent reviews that discuss myoblast fusion in Drosophila, each with their own perspective on the process . With apologies, we use gene nomenclature as specified by Flybase (http://flybase.org) but provide Table 1 with alternative names and references.

  4. Progress in understanding the Drosophila dnc locus.

    Science.gov (United States)

    Nighorn, A; Qiu, Y; Davis, R L

    1994-05-01

    The genetic dissection of learning and memory in Drosophila is two decades old. Recently, a great deal of progress has been made towards isolating new mutants as well as towards a better understanding of the originally isolated ones. This paper reviews the recent developments in the understanding of the structure and function of the gene identified by the first and best-characterized of these mutants, the Drosophila dunce mutant.

  5. Modeling tumor invasion and metastasis in Drosophila

    OpenAIRE

    2011-01-01

    Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabli...

  6. Early development of Chondrus ocellatus Holm (Gigartinaceae,Rhodophyta)

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Chondrus is an economically important red algae widely used for food and biochemical purpose. It early development is crucial for the culture and seedling propagation. We chose tetraspores and carpospores of Chondrus ocellatus as examples for experiment of the culture, induction and release in laboratory condition, aiming to understand early development of C. ocellatus and to apply in seedling production. Mature C. ocellatus were collected in Qingdao, China, from Nov. to Dec. 2004. After the gametophyte and tetrasporophyte were brushed and washed with sterilized seawater, the algal materials were treated in 1.5% KI for 20 min, then were dried for 1 h to stimulate the releasing of spores. After the spores released overnight, it and recording under microscope were carried out. Continuous observation of the early development showed that both tetraspore and carpospore are similar to each other. In general, three stages of the early development were shown being division, discoid crust and seedling stages. To the division stage, the most obvious feature was the increasing of cell number; during the discoid crust stage, the discoid crust had a three-dimensional axis, and it began to differentiate into two types of cells: the basal cells and the apical cells; and to the seedling stage, several protuberances-like appeared on the discoid crusts and formed juvenile seedlings. Carpospores and tetraspores exhibited a similar development process that included division stage, discoid crust stage and seedling stage.

  7. OTX2 and CRX rescue overlapping and photoreceptor‐specific functions in the Drosophila eye

    National Research Council Canada - National Science Library

    Terrell, David; Xie, Baotong; Workman, Michael; Mahato, Simpla; Zelhof, Andrew; Gebelein, Brian; Cook, Tiffany

    2012-01-01

    .... Drosophila encodes a single Otd factor that has multiple functions during eye development. Using the Drosophila eye as a model, we tested the ability of the human OTX1, OTX2, and CRX genes, as well as several disease...

  8. Characterization of Autophagic Responses in Drosophila melanogaster.

    Science.gov (United States)

    Xu, T; Kumar, S; Denton, D

    2017-01-01

    Drosophila is an excellent model system for studying autophagy during animal development due to the availability of genetic reagents and opportunity for in vivo cell biological analysis. The regulation and mechanism of autophagy are highly evolutionarily conserved and the role of autophagy has been characterized during various stages of Drosophila development as well as following starvation. Studies in Drosophila have revealed novel insights into the role of distinct components of the autophagy machinery. This chapter describes protocols for examining autophagy during Drosophila development. A crucial step in the induction of autophagy is the incorporation of Atg8a into the autophagosome. This can be measured as autophagic puncta using live fluorescent imaging, immunostaining, or immunoblot analysis of LC3/Atg8a processing. The level of autophagy can also be examined using other specific components of the autophagy pathway as markers detected by immunofluorescent imaging. Based on the distinct morphology of autophagy, it can also be examined by transmission electron microscopy. In addition, one of the advantages of using Drosophila as a model is the ability to undertake genetic analysis of individual components of the autophagy machinery. Current approaches that can be used to monitor autophagy, including the overall flux and individual steps in Drosophila melanogaster, will be discussed. © 2017 Elsevier Inc. All rights reserved.

  9. Understanding Autoinhibition of Drosophila Formin Cappuccino in vitro and in vivo

    OpenAIRE

    Bor, Batbileg

    2014-01-01

    Cappuccino (Capu) is an actin assembly factor that is necessary to establish Drosophila oocyte polarity. Disrupting normal polarity leads to female sterility. It is thought that Capu helps establish oocyte polarity by creating a mesh-like actin structure that spans the oocyte during early stages of development. Disappearance of this actin mesh in later stages of oogenesis coincides with rapid coordinated flows of the cytoplasm, referred to as cytoplasmic streaming. When cytoplasmic streaming ...

  10. Direct interaction between two actin nucleators is required in Drosophila oogenesis

    OpenAIRE

    Quinlan, Margot E.

    2013-01-01

    Controlled actin assembly is crucial to a wide variety of cellular processes, including polarity establishment during early development. The recently discovered actin mesh, a structure that traverses the Drosophila oocyte during mid-oogenesis, is essential for proper establishment of the major body axes. Genetic experiments indicate that at least two proteins, Spire (Spir) and Cappuccino (Capu), are required to build this mesh. The spire and cappuccino genetic loci were first identified as ma...

  11. Predictors of Early versus Later Spelling Development in Danish

    Science.gov (United States)

    Nielsen, Anne-Mette Veber; Juul, Holger

    2016-01-01

    The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

  12. Changing the Perspective on Early Development of Rett Syndrome

    Science.gov (United States)

    Marschik, Peter B.; Kaufmann, Walter E.; Sigafoos, Jeff; Wolin, Thomas; Zhang, Dajie; Bartl-Pokorny, Katrin D.; Pini, Giorgio; Zappella, Michele; Tager-Flusberg, Helen; Einspieler, Christa; Johnston, Michael V.

    2013-01-01

    We delineated the achievement of early speech-language milestones in 15 young children with Rett syndrome ("MECP2" positive) in the first two years of life using retrospective video analysis. By contrast to the commonly accepted concept that these children are normal in the pre-regression period, we found markedly atypical development of…

  13. Early Intervention and Its Effects on Maternal and Child Development.

    Science.gov (United States)

    Slaughter, Diana T.

    1983-01-01

    The longitudinal study reported used an intervention strategy to test the thesis that sociocultural background, mediated by maternal attitudes and behaviors, influences Black children's early development in educationally significant ways. Two models of parent education were contrasted: the Levenstein toy demonstration program and the…

  14. Early Journals and Their Influences on the Development of Gerontology

    Science.gov (United States)

    Mercer, Lorraine; Carter, Lorraine

    2012-01-01

    This examination of early gerontology journals identifies the multidisciplinary backgrounds of contributors, methods of investigation, nascent theory development, and formative themes and controversies. Through use of content, thematic, and critical analyses of second year issues of "The Gerontologist," "Educational Gerontology," "Research on…

  15. Early Childhood Education for Sustainability: Recommendations for Development

    Science.gov (United States)

    Daries, Julie; Engdahl, Ingrid; Otieno, Lorraine; Pramling-Samuelson, Ingrid; Siraj-Blatchford, John; Vallabh, Priya

    2009-01-01

    The following recommendations for "Education for Sustainable Development (ESD)" in Early Childhood Education were the product of an extended international collaboration that was supported by a number of bodies including the Centre for Environment and Sustainability in Gothenburg, the Swedish Ministry of Education and Research, the…

  16. Early Childhood Traumatic Brain Injuries: Effects on Development and Interventions.

    Science.gov (United States)

    Lowenthal, Barbara

    1998-01-01

    Describes the variety of possible effects of traumatic brain injuries (TBI) on early childhood development in the cognitive, language, social-emotional, motor, and adaptive domains. Suggests interventions which can assist young survivors and their families. Suggests that more long-term, intensive studies be conducted on the short- and long-term…

  17. Early Journals and Their Influences on the Development of Gerontology

    Science.gov (United States)

    Mercer, Lorraine; Carter, Lorraine

    2012-01-01

    This examination of early gerontology journals identifies the multidisciplinary backgrounds of contributors, methods of investigation, nascent theory development, and formative themes and controversies. Through use of content, thematic, and critical analyses of second year issues of "The Gerontologist," "Educational Gerontology," "Research on…

  18. Career Planning and Development for Early-Career Scientists

    Science.gov (United States)

    Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

  19. Regionalism and Development in Early Nineteenth Century Spanish America.

    Science.gov (United States)

    Friedman, Douglas

    An understanding of regionalism in early 19th century Spanish America is crucial to any understanding of this region's economic development. Regionalism became the barrier to the kind of integrated national economy that some writers claim could have been implemented had it not been for the imposition of dependency by external forces. This…

  20. More Alike than Different: Early Childhood Professional Development in Guatemala

    Science.gov (United States)

    Hardin, Belinda J.; Vardell, Rosemarie; de Castaneda, Albertina

    2008-01-01

    This article describes an early childhood professional development project that took place in the summer of 2005 in Guatemala City. Located in Central America, Guatemala has a population of approximately 12.3 million people, including more than two million children under the age of 5 (UNESCO Institute for Statistics, 2007; UNICEF, 2004). Events…

  1. Developing Early Undergraduate Research at a Two-Year College

    Science.gov (United States)

    Sibbernsen, Kendra

    2013-01-01

    Two-year college (TYC) physics teachers are not often required to provide student research experiences as a part of their contracted duties. However, some TYC physics faculty members are interested in developing research opportunities for their freshman- and sophomore-level students, often called "early undergraduate research" (EUR).…

  2. Early Embryo Survival and Development in Sows with Lactational Ovulation

    NARCIS (Netherlands)

    Gerritsen, R.; Soede, N.M.; Langendijk, P.; Taverne, M.A.M.; Kemp, B.

    2008-01-01

    During lactation, daily separation of sow and piglets, intermittent suckling (IS), can induce lactational oestrus and ovulation. This study examined effects of IS on subsequent early embryo survival and development. Multiparous Topigs40 sows were separated from their piglets for either 12 consecutiv

  3. Impact of early pregnancy on prenatal development in the pig

    NARCIS (Netherlands)

    Lende, van der T.

    1989-01-01

    In the present study aspects of the impact of early pregnancy on the average prenatal development per litter and on the within-litter weight distribution at birth have been investigated. The aims of the present study are given in the introduction (chapter 1). A brief review of the literatur

  4. Illumina Spin-off to Develop Early-Detection Test.

    Science.gov (United States)

    Colwell, Janet

    2016-04-01

    DNA-sequencing giant Illumina has formed a new company, called Grail, to develop liquid biopsies capable of spotting cancer before symptoms arise. The start-up is working on a low-cost "pan-cancer" test that can detect multiple cancer types early, which it hopes to introduce by 2019.

  5. Reflecting on Early Literacy Development in the Context of Vanuatu

    Science.gov (United States)

    Hughes, Desma

    2004-01-01

    A low level of literacy development plagues many parts of the Pacific region despite the fact that parents are very keen for their children to become literate in order to embrace the modern world. Issues concerning early education and the attainment of literacy are still a challenge in the Pacific. In order to understand the reasons for the low…

  6. Early retinoic acid deprivation in developing zebrafish results in microphthalmia.

    Science.gov (United States)

    Le, Hong-Gam T; Dowling, John E; Cameron, D Joshua

    2012-09-01

    Vitamin A deficiency causes impaired vision and blindness in millions of children around the world. Previous studies in zebrafish have demonstrated that retinoic acid (RA), the acid form of vitamin A, plays a vital role in early eye development. The objective of this study was to describe the effects of early RA deficiency by treating zebrafish with diethylaminobenzaldehyde (DEAB), a potent inhibitor of the enzyme retinaldehyde dehydrogenase (RALDH) that converts retinal to RA. Zebrafish embryos were treated for 2 h beginning at 9 h postfertilization. Gross morphology and retinal development were examined at regular intervals for 5 days after treatment. The optokinetic reflex (OKR) test, visual background adaptation (VBA) test, and the electroretinogram (ERG) were performed to assess visual function and behavior. Early treatment of zebrafish embryos with 100 μM DEAB (9 h) resulted in reduced eye size, and this microphthalmia persisted through larval development. Retinal histology revealed that DEAB eyes had significant developmental abnormalities but had relatively normal retinal lamination by 5.5 days postfertilization. However, the fish showed neither an OKR nor a VBA response. Further, the retina did not respond to light as measured by the ERG. We conclude that early deficiency of RA during eye development causes microphthalmia as well as other visual defects, and that timing of the RA deficiency is critical to the developmental outcome.

  7. Predictors of Early versus Later Spelling Development in Danish

    Science.gov (United States)

    Nielsen, Anne-Mette Veber; Juul, Holger

    2016-01-01

    The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

  8. Early development of synchrony in cortical activations in the human.

    Science.gov (United States)

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates.

  9. Modeling tumor invasion and metastasis in Drosophila

    Directory of Open Access Journals (Sweden)

    Wayne O. Miles

    2011-11-01

    Full Text Available Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis.

  10. Modeling tumor invasion and metastasis in Drosophila.

    Science.gov (United States)

    Miles, Wayne O; Dyson, Nicholas J; Walker, James A

    2011-11-01

    Conservation of major signaling pathways between humans and flies has made Drosophila a useful model organism for cancer research. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Several recent high profile studies have examined the processes constraining the metastatic growth of tumor cells in fruit fly models. Cell invasion can be studied in the context of an in vivo setting in flies, enabling the genetic requirements of the microenvironment of tumor cells undergoing metastasis to be analyzed. This Perspective discusses the strengths and limitations of Drosophila models of cancer invasion and the unique tools that have enabled these studies. It also highlights several recent reports that together make a strong case for Drosophila as a system with the potential for both testing novel concepts in tumor progression and cell invasion, and for uncovering players in metastasis.

  11. Early life environment and the developing cardiovascular system

    OpenAIRE

    Idris, N.S.

    2015-01-01

    Background The dynamics of cardiovascular system development in childhood are still largely unknown. Despite its known sensitivity to small perturbations, it has not been fully elucidated how the cardiovascular system evolves and responds to different stimuli and how these impact the future cardiovascular status. This thesis is basically aimed at exploring the effects of several possible postnatal determinantson the developing cardiovascular system. These early life determinants perhaps immed...

  12. Zebrafish in the Study of Early Cardiac Development

    OpenAIRE

    Liu, Jiandong; Stainier, Didier Y.R.

    2012-01-01

    Heart development is a complex process that involves cell specification and differentiation, as well as elaborate tissue morphogenesis and remodeling, to generate a functional organ. The zebrafish has emerged as a powerful model system to unravel the basic genetic, molecular and cellular mechanisms of cardiac development and function. Here we summarize and discuss recent discoveries on early cardiac specification and the identification of the second heart field in zebrafish. In addition to th...

  13. Altered anterior visual system development following early monocular enucleation

    Directory of Open Access Journals (Sweden)

    Krista R. Kelly

    2014-01-01

    Conclusions: The novel finding of an asymmetry in morphology of the anterior visual system following long-term survival from early monocular enucleation indicates altered postnatal visual development. Possible mechanisms behind this altered development include recruitment of deafferented cells by crossing nasal fibres and/or geniculate cell retention via feedback from primary visual cortex. These data highlight the importance of balanced binocular input during postnatal maturation for typical anterior visual system morphology.

  14. Does copepods influence dusky grouper (Epinephelus marginatus early development?

    Directory of Open Access Journals (Sweden)

    Monica Mateus

    2014-06-01

    Full Text Available Good knowledge on the development of early life stages is essential for successful conservation programs of threatened fish species. Diet and rearing system affects early life survival and juvenile quality. Copepods are the natural food of fish larvae in the wild possessing high nutritional value, when compared with live feeds used in aquaculture (rotifers and artemia, and a wide range of size classes. Rearing systems with low water column disturbance and low larval densities enhanced the survival of fragile fish larvae. The aim of this work is to evaluate the effect of the introduction of copepods in the diet of early dusky grouper larvae reared in controlled mesocosm systems using larval development and juvenile quality as indicators. Two feeding protocols were tested, one composed only by rotifers (Brachionus plicatilis, brine shrimp (Artemia spp. and dry feed and the other supplemented with copepods (Paracartia grani from mouth opening (2 day after hatching - DAH to 8 DAH. Feeding behavior, growth, survival, skeletal malformations and digestive enzymes activity was assessed at different developmental stages. The addition of copepods to the early larvae diet of dusky grouper resulted in faster development and higher survival rates. Larvae fed with copepods improved their development. At 20 DAH all larvae reared at the mesocosm with copedods were already at the stage of post-flexion while in the system without copepods this stage was attained later. At 25 DAH only 64% of the larvae were in post flexion in the mesoscosm without copepods. At 30 DAH larvae supplemented with copepods attained an acidic digestion (high specific activity of pepsin earlier than at the system without copepods. In this last system alkaline digestion (trypsin specific activity, characteristic of early larval stages, was significantly higher reinforcing the faster development of larvae fed with copepods. In both systems the incidence of skeletal malformations was low.

  15. Evolutionary origins and early development of number processing

    CERN Document Server

    Geary, David C; Mann Koepke, Kathleen

    2014-01-01

    The first volume in this ground-breaking series focuses on the origins and early development of numerical cognition in non-human primates, lower vertebrates, human infants, and preschool children. The text will help readers understand the nature and complexity of these foundational quantitative concepts and skills along with evolutionary precursors and early developmental trajectories. Brings together and focuses the efforts and research of multiple disciplines working in math cognition.The contributors bring vast knowledge and experience to bear on resolving extant

  16. Multiple domains of Stardust differentially mediate localisation of the Crumbs-Stardust complex during photoreceptor development in Drosophila.

    Science.gov (United States)

    Bulgakova, Natalia A; Kempkens, Ozlem; Knust, Elisabeth

    2008-06-15

    Drosophila Stardust (Sdt), a member of the MAGUK family of scaffolding proteins, is a constituent of the evolutionarily conserved Crumbs-Stardust (Crb-Sdt) complex that controls epithelial cell polarity in the embryo and morphogenesis of photoreceptor cells. Although apical localisation is a hallmark of the complex in all cell types and in all organisms analysed, only little is known about how individual components are targeted to the apical membrane. We have performed a structure-function analysis of Sdt by constructing transgenic flies that express altered forms of Sdt to determine the roles of individual domains for localisation and function in photoreceptor cells. The results corroborate the observation that the organisation of the Crb-Sdt complex is differentially regulated in pupal and adult photoreceptors. In pupal photoreceptors, only the PDZ domain of Sdt - the binding site of Crb - is required for apical targeting. In adult photoreceptors, by contrast, targeting of Sdt to the stalk membrane, a distinct compartment of the apical membrane between the rhabdomere and the zonula adherens, depends on several domains, and seems to be a two-step process. The N-terminus, including the two ECR domains and a divergent N-terminal L27 domain that binds the multi-PDZ domain protein PATJ in vitro, is necessary for targeting the protein to the apical pole of the cell. The PDZ-, the SH3- and the GUK-domains are required to restrict the protein to the stalk membrane. Drosophila PATJ or Drosophila Lin-7 are stabilised whenever a Sdt variant that contains the respective binding site is present, independently of where the variant is localised. By contrast, only full-length Sdt, confined to the stalk membrane, stabilises and localises Crb, although only in reduced amounts. The amount of Crumbs recruited to the stalk membrane correlates with its length. Our results highlight the importance of the different Sdt domains and point to a more intricate regulation of the Crb

  17. Early vocabulary development in children with bilateral cochlear implants.

    Science.gov (United States)

    Välimaa, Taina; Kunnari, Sari; Laukkanen-Nevala, Päivi; Lonka, Eila

    2017-06-16

    Children with unilateral cochlear implants (CIs) may have delayed vocabulary development for an extended period after implantation. Bilateral cochlear implantation is reported to be associated with improved sound localization and enhanced speech perception in noise. This study proposed that bilateral implantation might also promote early vocabulary development. Knowledge regarding vocabulary growth and composition in children with bilateral CIs and factors associated with it may lead to improvements in the content of early speech and language intervention and family counselling. To analyse the growth of early vocabulary and its composition during the first year after CI activation and to investigate factors associated with vocabulary growth. The participants were 20 children with bilateral CIs (12 boys; eight girls; mean age at CI activation = 12.9 months). Vocabulary size was assessed with the Finnish version of the MacArthur Communicative Development Inventories (CDI) Infant Form and compared with normative data. Vocabulary composition was analysed in relation to vocabulary size. Growth curve modelling was implemented using a linear mixed model to analyse the effects of the following variables on early vocabulary growth: time, gender, maternal education, residual hearing with hearing aids, age at first hearing aid fitting and age at CI activation. Despite clear vocabulary growth over time, children with bilateral CIs lagged behind their age norms in receptive vocabulary during the first 12 months after CI activation. In expressive vocabulary, 35% of the children were able to catch up with their age norms, but 55% of the children lagged behind them. In receptive and expressive vocabularies of 1-20 words, analysis of different semantic categories indicated that social terms constituted the highest proportion. Nouns constituted the highest proportion in vocabularies of 101-400 words. The proportion of verbs remained below 20% and the proportion of function words and

  18. Development of Early Warning Methods for Electric Power Systems

    DEFF Research Database (Denmark)

    Jóhannsson, Hjörtur

    This thesis concerns the development of methods that can provide, in realtime, an early warning for an emerging blackout in electric power systems. The blackout in E-Denmark and S-Sweden on September 23, 2003 is the main motivation for the method development. The blackout was caused by occurrence...... methods, that could, in such situations, give an early warning for the emerging blackout. After investigation of data and plots taken from the time of the blackout, it was decided to focus the development on assessment of aperiodic small signal stability. In order to assess the system generators aperiodic...... small signal stability, expressions for stability boundaries were algebraically derived in the injection impedance plane. A method for detecting aperiodic small signal stability was established, which was based on one of the derived boundaries. The method carries out an element-wise assessment...

  19. Early childhood WIC participation, cognitive development and academic achievement.

    Science.gov (United States)

    Jackson, Margot I

    2015-02-01

    For the 22% of American children who live below the federal poverty line, and the additional 23% who live below twice that level, nutritional policy is part of the safety net against hunger and its negative effects on children's development. The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) provides steadily available food from the food groups essential for physical and cognitive development. The effects of WIC on dietary quality among participating women and children are strong and positive. Furthermore, there is a strong influence of nutrition on cognitive development and socioeconomic inequality. Yet, research on the non-health effects of U.S. child nutritional policy is scarce, despite the ultimate goal of health policies directed at children-to enable productive functioning across multiple social institutions over the life course. Using two nationally representative, longitudinal surveys of children-the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B) and the Child Development Supplement (CDS) of the Panel Study of Income Dynamics-I examine how prenatal and early childhood exposure to WIC is associated in the short-term with cognitive development, and in the longer-term with reading and math learning. Results show that early WIC participation is associated with both cognitive and academic benefits. These findings suggest that WIC meaningfully contributes to children's educational prospects.

  20. The effect of TiO{sub 2} and Ag nanoparticles on reproduction and development of Drosophila melanogaster and CD-1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Philbrook, Nicola A., E-mail: 3nap@queensu.ca [School of Environmental Studies, Biosciences Complex, Queen' s University, 116 Barrie Street, Kingston, Ontario, Canada K7L 3N6 (Canada); Department of Biomedical and Molecular Sciences, Botterell Hall, 5th Floor, Queen' s University, 18 Stuart Street, Kingston, Ontario, Canada K7L 3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [School of Environmental Studies, Biosciences Complex, Queen' s University, 116 Barrie Street, Kingston, Ontario, Canada K7L 3N6 (Canada); Department of Biomedical and Molecular Sciences, Botterell Hall, 5th Floor, Queen' s University, 18 Stuart Street, Kingston, Ontario, Canada K7L 3N6 (Canada); Afrooz, A.R.M. Nabiul [Department of Civil and Environmental Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States); Saleh, Navid B., E-mail: salehn@cec.sc.edu [Department of Civil and Environmental Engineering, University of South Carolina, 300 Main Street, Columbia, SC 29208 (United States); Walker, Virginia K., E-mail: walkervk@queensu.ca [School of Environmental Studies, Biosciences Complex, Queen' s University, 116 Barrie Street, Kingston, Ontario, Canada K7L 3N6 (Canada); Department of Biology, Biosciences Complex, Queen' s University, 116 Barrie Street, Kingston, Ontario, Canada K7L 3N6 (Canada)

    2011-12-15

    In the last two decades, nanoparticles (NPs) have found applications in a wide variety of consumer goods. Titanium dioxide (TiO{sub 2}) and silver (Ag) NPs are both found in cosmetics and foods, but their increasing use is of concern due to their ability to be taken up by biological systems. While there are some reports of TiO{sub 2} and Ag NPs affecting complex organisms, their effects on reproduction and development have been largely understudied. Here, the effects of orally administered TiO{sub 2} or Ag NPs on reproduction and development in two different model organisms were investigated. TiO{sub 2} NPs reduced the developmental success of CD-1 mice after a single oral dose of 100 or 1000 mg/kg to dams, resulting in a statistically significant increase in fetal deformities and mortality. Similarly, TiO{sub 2} NP addition to food led to a significant progeny loss in the fruit fly, Drosophila, as shown by a decline in female fecundity. Ag NP administration resulted in an increase in the mortality of fetal mice. Similarly in Drosophila, Ag NP feeding led to a significant decrease in developmental success, but unlike TiO{sub 2} NP treatment, there was no decline in fecundity. The distinct response associated with each type of NP likely reflects differences in NP administration as well as the biology of the particular model. Taken together, however, this study warns that these common NPs could be detrimental to the reproductive and developmental health of both invertebrates and vertebrates.

  1. Prostaglandins temporally regulate cytoplasmic actin bundle formation during Drosophila oogenesis.

    Science.gov (United States)

    Spracklen, Andrew J; Kelpsch, Daniel J; Chen, Xiang; Spracklen, Cassandra N; Tootle, Tina L

    2014-02-01

    Prostaglandins (PGs)--lipid signals produced downstream of cyclooxygenase (COX) enzymes--regulate actin dynamics in cell culture and platelets, but their roles during development are largely unknown. Here we define a new role for Pxt, the Drosophila COX-like enzyme, in regulating the actin cytoskeleton--temporal restriction of actin remodeling during oogenesis. PGs are required for actin filament bundle formation during stage 10B (S10B). In addition, loss of Pxt results in extensive early actin remodeling, including actin filaments and aggregates, within the posterior nurse cells of S9 follicles; wild-type follicles exhibit similar structures at a low frequency. Hu li tai shao (Hts-RC) and Villin (Quail), an actin bundler, localize to all early actin structures, whereas Enabled (Ena), an actin elongation factor, preferentially localizes to those in pxt mutants. Reduced Ena levels strongly suppress early actin remodeling in pxt mutants. Furthermore, loss of Pxt results in reduced Ena localization to the sites of bundle formation during S10B. Together these data lead to a model in which PGs temporally regulate actin remodeling during Drosophila oogenesis by controlling Ena localization/activity, such that in S9, PG signaling inhibits, whereas at S10B, it promotes Ena-dependent actin remodeling.

  2. [Dental caries and early childhood development: a pilot study].

    Science.gov (United States)

    Núñez, F Loreto; Sanz, B Javier; Mejía, L Gloria

    2015-01-01

    To investigate the association between dental caries and early childhood development in 3-year-olds from Talca, Chile. A pilot study with a convenience sample of 3-year-olds from Talca (n = 39) who attend public healthcare centers. Child development was measured by the Psychomotor Development Index (PDI), a screening tool used nationally among pre-school children to assess language development, fine motor skills and coordination areas. Dental caries prevalence was evaluated by decayed, missing, filled teeth (DFMT) and decayed, missing, filled tooth surfaces (DFMS) ceo-d and ceo-s indexes. The children were divided into two groups according to the PDIscore: those with a score of 40 or more were considered developmentally normal (n = 32), and those with a score below 40 were considered as having impaired development (n = 7). The severity of caries (DMFT) was negatively correlated with PDI (r = -0.82), and children with the lowest TEPSI score had the highest DFMT values. The average DMFT in children with normal development was 1.31, and 3.57 for those with impaired development. This pilot study indicates that the severity of dental caries is correlated with early childhood development. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  3. Early Bifrontal Brain Injury: Disturbances in Cognitive Function Development

    Directory of Open Access Journals (Sweden)

    Christine Bonnier

    2010-01-01

    Full Text Available We describe six psychomotor, language, and neuropsychological sequential developmental evaluations in a boy who sustained a severe bifrontal traumatic brain injury (TBI at 19 months of age. Visuospatial, drawing, and writing skills failed to develop normally. Gradually increasing difficulties were noted in language leading to reading and spontaneous speech difficulties. The last two evaluations showed executive deficits in inhibition, flexibility, and working memory. Those executive abnormalities seemed to be involved in the other impairments. In conclusion, early frontal brain injury disorganizes the development of cognitive functions, and interactions exist between executive function and other cognitive functions during development.

  4. A Drosophila Model for Screening Antiobesity Agents

    Directory of Open Access Journals (Sweden)

    Tran Thanh Men

    2016-01-01

    Full Text Available Although triacylglycerol, the major component for lipid storage, is essential for normal physiology, its excessive accumulation causes obesity in adipose tissue and is associated with organ dysfunction in nonadipose tissue. Here, we focused on the Drosophila model to develop therapeutics for preventing obesity. The brummer (bmm gene in Drosophila melanogaster is known to be homologous with human adipocyte triglyceride lipase, which is related to the regulation of lipid storage. We established a Drosophila model for monitoring bmm expression by introducing the green fluorescent protein (GFP gene as a downstream reporter of the bmm promoter. The third-instar larvae of Drosophila showed the GFP signal in all tissues observed and specifically in the salivary gland nucleus. To confirm the relationship between bmm expression and obesity, the effect of oral administration of glucose diets on bmm promoter activity was analyzed. The Drosophila flies given high-glucose diets showed higher lipid contents, indicating the obesity phenotype; this was suggested by a weaker intensity of the GFP signal as well as reduced bmm mRNA expression. These results demonstrated that the transgenic Drosophila model established in this study is useful for screening antiobesity agents. We also report the effects of oral administration of histone deacetylase inhibitors and some vegetables on the bmm promoter activity.

  5. Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life

    Science.gov (United States)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2007-01-01

    The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.3.9 Gy., (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

  6. Genotype and environment shape the fitness of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Wesam S. Meshrif

    2015-01-01

    Full Text Available Fitness traits of Drosophila are believed to be expressed under genetic control and the environment. This study focuses on the interaction between the genotype (expressing high and low fitness level of Drosophila melanogaster and the environment (diet and infection. The environmental factors are supposed to modify traits such as the survival rate, development time, adult dry weight and response to microbial infection. The results indicated that yeast species (nutrients, bacterial infection and the genotype of Drosophila affected the survival rates and the development time of Drosophila. The fit Drosophila produces more survivors and develops faster than the unfit one. The yeast, Pichia toletana induced the highest survival and the fastest development of Drosophila, while Metschnikowia pulcherrima induced the opposite. The origin also had an effect on the development time; the African lines developed faster than the European ones. The yeast species and its concentration appeared to affect the dry weight of Drosophila too. Following infection with Pseudomonas stutzeri, several antimicrobial peptides, such as drosomycin and metchnikowin have been activated in Drosophila adults when they feed on less nutritive yeast (M. pulcherrima. The above mentioned results support the capacity of genotype-by-environment interactions to shape the fitness of D. melanogaster, where the contribution of each factor may differ according to the trait observed and the population under investigation.

  7. Priorities for early childhood development in low-income countries.

    Science.gov (United States)

    Olusanya, Bolajoko O

    2011-01-01

    The remarkable progress in reducing child mortality in low-income countries is now accompanied with a rapidly expanding population of child survivors and increased life expectancy. However, many have special health care needs in the early foundational years for optimal health and educational and vocational status. Investment in early childhood development (ECD) is therefore crucial but likely to be constrained by lack of adequate resources making priority-setting inevitable. A review of current ECD approaches in sub-Saharan Africa and South Asia shows that concerted multidisciplinary and cross-sectoral initiatives targeted at children with developmental disabilities across all crucial domains of ECD and guided by available evidence on optimal timing for interventions are urgently required. This focus would necessitate appropriate national ECD policies, modifications to the current global ECD programs in the developing world, and a more active collaboration between pediatricians and other related service providers.

  8. EARLY DEVELOPMENT OF SPEECH AND INTERACTION BETWEEN MOTHER AND CHILD

    OpenAIRE

    Ana RADOJKOVIC; Slavica GOLUBOVIC; Dejan RADOJKOVIC

    1998-01-01

    Respecting the opinions of the modern researches which show that early interaction between mother and child has the crucial importance in child’s development, almost in all parts of child’s functions (speech, emotions, motor functions, intelligence). The authors did their own research that does not diffuse from the result got from former researches.Although this research is related to normal population of the children, also it is very important for speech in context of interaction between mot...

  9. Gravity from strings: personal reminiscence on early developments

    CERN Document Server

    Yoneya, Tamiaki

    2009-01-01

    I discuss the early developments of string theory with respect to its connection with gauge theory and general relativity from my own perspective. The period covered is mainly from 1969 to 1974, during which I became involved in research on dual string models as a graduate student. My thinking towards the recognition of string theory as an extended quantum theory of gravity is described. Some retrospective remarks on my later works related to this subject are also given.

  10. Dynamic Self-Organization and Early Lexical Development in Children

    Science.gov (United States)

    Li, Ping; Zhao, Xiaowei; Whinney, Brian Mac

    2007-01-01

    In this study we present a self-organizing connectionist model of early lexical development. We call this model DevLex-II, based on the earlier DevLex model. DevLex-II can simulate a variety of empirical patterns in children's acquisition of words. These include a clear vocabulary spurt, effects of word frequency and length on age of acquisition,…

  11. Early embryonic development and transplantation in tree shrews

    OpenAIRE

    YAN, Lan-Zhen; Sun, Bin; LYU, Long-Bao; MA, Yu-Hua; Chen, Jia-Qi; Lin, Qing; Zheng, Ping; Zhao, Xu-dong

    2016-01-01

    As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 femal...

  12. The Mapping of Predicted Triplex DNA:RNA in the Drosophila Genome Reveals a Prominent Location in Development- and Morphogenesis-Related Genes

    Directory of Open Access Journals (Sweden)

    Claude Pasquier

    2017-07-01

    Full Text Available Double-stranded DNA is able to form triple-helical structures by accommodating a third nucleotide strand. A nucleic acid triplex occurs according to Hoogsteen rules that predict the stability and affinity of the third strand bound to the Watson–Crick duplex. The “triplex-forming oligonucleotide” (TFO can be a short sequence of RNA that binds to the major groove of the targeted duplex only when this duplex presents a sequence of purine or pyrimidine bases in one of the DNA strands. Many nuclear proteins are known to bind triplex DNA or DNA:RNA, but their biological functions are unexplored. We identified sequences that are capable of engaging as the “triplex-forming oligonucleotide” in both the pre-lncRNA and pre-mRNA collections of Drosophila melanogaster. These motifs were matched against the Drosophila genome in order to identify putative sequences of triplex formation in intergenic regions, promoters, and introns/exons. Most of the identified TFOs appear to be located in the intronic region of the analyzed genes. Computational prediction of the most targeted genes by TFOs originating from pre-lncRNAs and pre-mRNAs revealed that they are restrictively associated with development- and morphogenesis-related gene networks. The refined analysis by Gene Ontology enrichment demonstrates that some individual TFOs present genome-wide scale matches that are located in numerous genes and regulatory sequences. The triplex DNA:RNA computational mapping at the genome-wide scale suggests broad interference in the regulatory process of the gene networks orchestrated by TFO RNAs acting in association simultaneously at multiple sites.

  13. Progress Developing the Kansas Early Childhood Special Education Accountability System: Initial Findings Using ECO and COSF

    Science.gov (United States)

    Greenwood, Charles R.; Walker, Dale; Hornbeck, Marguerite; Hebbeler, Kathleen; Spiker, Donna

    2007-01-01

    Policy decision makers, early educators, and early interventionists face numerous challenges as they develop and implement statewide accountability systems to evaluate and improve children's early intervention and early childhood special education outcomes. Kansas was an early adopter of the Child Outcomes Summary Form (COSF) developed by the…

  14. Development of tsunami early warning systems and future challenges

    Directory of Open Access Journals (Sweden)

    J. Wächter

    2012-06-01

    Full Text Available Fostered by and embedded in the general development of information and communications technology (ICT, the evolution of tsunami warning systems (TWS shows a significant development from seismic-centred to multi-sensor system architectures using additional sensors (e.g. tide gauges and buoys for the detection of tsunami waves in the ocean.

    Currently, the beginning implementation of regional tsunami warning infrastructures indicates a new phase in the development of TWS. A new generation of TWS should not only be able to realise multi-sensor monitoring for tsunami detection. Moreover, these systems have to be capable to form a collaborative communication infrastructure of distributed tsunami warning systems in order to implement regional, ocean-wide monitoring and warning strategies.

    In the context of the development of the German Indonesian Tsunami Early Warning System (GITEWS and in the EU-funded FP6 project Distant Early Warning System (DEWS, a service platform for both sensor integration and warning dissemination has been newly developed and demonstrated. In particular, standards of the Open Geospatial Consortium (OGC and the Organization for the Advancement of Structured Information Standards (OASIS have been successfully incorporated.

    In the FP7 project Collaborative, Complex and Critical Decision-Support in Evolving Crises (TRIDEC, new developments in ICT (e.g. complex event processing (CEP and event-driven architecture (EDA are used to extend the existing platform to realise a component-based technology framework for building distributed tsunami warning systems.

  15. Sonic hedgehog expression during early tooth development in Suncus murinus.

    Science.gov (United States)

    Miyado, Mami; Ogi, Hidenao; Yamada, Gen; Kitoh, Junzo; Jogahara, Takamichi; Oda, Sen-Ichi; Sato, Iwao; Miyado, Kenji; Sunohara, Masataka

    2007-11-16

    Tooth development is a highly organized process characterized by reciprocal interactions between epithelium and mesenchyme. However, the expression patterns and functions of molecules involved in mouse tooth development are unclear from the viewpoint of explaining human dental malformations and anomalies. Here, we show the expression of sonic hedgehog (Shh), a potent initiator of morphogenesis, during the early stages of tooth development in Suncus murinus. Initially, symmetrical, elongated expression of suncus Shh (sShh) was observed in the thin layer of dental epithelial cells along the mesial-distal axis of both jaws. As the dental epithelium continued to develop, sShh was strictly restricted to the predicted leading parts of the growing, invaginating epithelium corresponding to tooth primordia and enamel knots. We propose that some aspects of Shh function in tooth development are widely conserved in mammalian phylogeny.

  16. Regulation and functions of the lms homeobox gene during development of embryonic lateral transverse muscles and direct flight muscles in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dominik Müller

    Full Text Available BACKGROUND: Patterning and differentiation of developing musculatures require elaborate networks of transcriptional regulation. In Drosophila, significant progress has been made into identifying the regulators of muscle development and defining their interactive networks. One major family of transcription factors involved in these processes consists of homeodomain proteins. In flies, several members of this family serve as muscle identity genes to specify the fates of individual muscles, or groups thereof, during embryonic and/or adult muscle development. Herein, we report on the expression and function of a new Drosophila homeobox gene during both embryonic and adult muscle development. METHODOLOGY/PRINCIPAL FINDINGS: The newly described homeobox gene, termed lateral muscles scarcer (lms, which has yet uncharacterized orthologs in other invertebrates and primitive chordates but not in vertebrates, is expressed exclusively in subsets of developing muscle tissues. In embryos, lms is expressed specifically in the four lateral transverse (LT muscles and their founder cells in each hemisegment, whereas in larval wing imaginal discs, it is expressed in myoblasts that develop into direct flight muscles (DFMs, which are important for proper wing positioning. We have analyzed the regulatory inputs of various other muscle identity genes with overlapping or complementary expression patterns towards the cell type specific regulation of lms expression. Further we demonstrate that lms null mutants exhibit reduced numbers of embryonic LT muscles, and null mutant adults feature held-out-wing phenotypes. We provide a detailed description of the pattern and morphology of the direct flight muscles in the wild type and lms mutant flies by using the recently-developed ultramicroscopy and show that, in the mutants, all DFMs are present and present normal morphologies. CONCLUSIONS/SIGNIFICANCE: We have identified the homeobox gene lms as a new muscle identity gene

  17. Development of an assisting detection system for early infarct diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Sim, K. S.; Nia, M. E.; Ee, C. S. [Faculty of Engineering and Technology, Multimedia University, Melaka (Malaysia)

    2015-04-24

    In this paper, a detection assisting system for early infarct detection is developed. This new developed method is used to assist the medical practitioners to diagnose infarct from computed tomography images of brain. Using this assisting system, the infarct could be diagnosed at earlier stages. The non-contrast computed tomography (NCCT) brain images are the data set used for this system. Detection module extracts the pixel data from NCCT brain images, and produces the colourized version of images. The proposed method showed great potential in detecting infarct, and helps medical practitioners to make earlier and better diagnoses.

  18. Gestural development and its relation to a child's early vocabulary.

    Science.gov (United States)

    Kraljević, Jelena Kuvač; Cepanec, Maja; Simleša, Sanja

    2014-05-01

    Gesture and language are tightly connected during the development of a child's communication skills. Gestures mostly precede and define the way of language development; even opposite direction has been found. Few recent studies have focused on the relationship between specific gestures and specific word categories, emphasising that the onset of one gesture type predicts the onset of certain word categories or of the earliest word combinations. The aim of this study was to analyse predicative roles of different gesture types on the onset of first word categories in a child's early expressive vocabulary. Our data show that different types of gestures predict different types of word production. Object gestures predict open-class words from the age of 13 months, and gestural routines predict closed-class words and social terms from 8 months. Receptive vocabulary has a strong mediating role for all linguistically defined categories (open- and closed-class words) but not for social terms, which are the largest word category in a child's early expressive vocabulary. Accordingly, main contribution of this study is to define the impact of different gesture types on early expressive vocabulary and to determine the role of receptive vocabulary in gesture-expressive vocabulary relation in the Croatian language. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Clinical assessment of early language development: a simplified short form of the Mandarin communicative development inventory.

    Science.gov (United States)

    Soli, Sigfrid D; Zheng, Yun; Meng, Zhaoli; Li, Gang

    2012-09-01

    The purpose of this study was to develop a practical mean for clinical evaluation of early pediatric language development by establishing developmental trajectories for receptive and expressive vocabulary growth in children between 6 and 32 months of age using a simple, time-efficient assessment tool. Simplified short form versions of the Words and Gestures and Words and Sentences vocabulary inventories in the Mandarin Communicative Development Inventory [1] were developed and used to assess early language development in developmentally normal children from 6 to 32 months of age during routine health checks. Developmental trajectories characterizing the rate of receptive and expressive vocabulary growth between 6 and 32 months of age are reported. These trajectories allow the equivalent age corresponding to a score to be determined after a brief structured interview with the child's parents that can be conducted in a busy clinical setting. The simplified short forms of the Mandarin Communicative Development Inventories can serve as a clinically useful tool to assess early child language development, providing a practical mean of objectively assessing early language development following early interventions to treat young children with hearing impairment as well as speech and language delays. Objective evidence of language development is essential for achievement of effective (re)habilitation outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Considerations in the early development of biosimilar products.

    Science.gov (United States)

    Li, Edward C; Abbas, Richat; Jacobs, Ira A; Yin, Donghua

    2015-05-01

    The widespread use and patent expiration of many biologics have led to global interest in development of biosimilar products. Because the manufacture of biologics, including biosimilars, is a complex process involving living systems, the development of a biosimilar is more rigorous than the development of a generic small molecule drug. Several regulatory agencies have established or are proposing guidelines that recommend a stepwise process to ensure the efficacy and safety of a biosimilar are highly similar to the reference product. This article also explores the early clinical phase of biosimilar development, which is particularly important to resolving any uncertainties that might remain following in vitro and in vivo evaluations and to enable a selective and targeted approach to Phase III clinical efficacy and safety investigation.

  1. Epigenetics and development of food allergy (FA) in early childhood.

    Science.gov (United States)

    Hong, Xiumei; Wang, Xiaobin

    2014-09-01

    This review aims to highlight the latest advance on epigenetics in the development of food allergy (FA) and to offer future perspectives. FA, a condition caused by an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, has emerged as a major clinical and public health problem worldwide in light of its increasing prevalence, potential fatality, and significant medical and economic impact. Current evidence supports that epigenetic mechanisms are involved in immune regulation and that the epigenome may represent a key "missing piece" of the etiological puzzle for FA. There are a growing number of population-based epigenetic studies on allergy-related phenotypes, mostly focused on DNA methylation. Previous studies mostly applied candidate-gene approaches and have demonstrated that epigenetic marks are associated with multiple allergic diseases and/or with early-life exposures relevant to allergy development (such as early-life smoking exposure, air pollution, farming environment, and dietary fat). Rapid technological advancements have made unbiased genome-wide DNA methylation studies highly feasible, although there are substantial challenge in study design, data analyses, and interpretation of findings. In conclusion, epigenetics represents both an important knowledge gap and a promising research area for FA. Due to the early onset of FA, epigenetic studies of FA in prospective birth cohorts have the potential to better understand gene-environment interactions and underlying biological mechanisms in FA during critical developmental windows (preconception, in utero, and early childhood) and may lead to new paradigms in the diagnosis, prevention, and management of FA and provide novel targets for future drug discovery and therapies for FA.

  2. Drosophila microRNAs 263a/b confer robustness during development by protecting nascent sense organs from apoptosis.

    Science.gov (United States)

    Hilgers, Valérie; Bushati, Natascha; Cohen, Stephen M

    2010-06-15

    miR-263a/b are members of a conserved family of microRNAs that are expressed in peripheral sense organs across the animal kingdom. Here we present evidence that miR-263a and miR-263b play a role in protecting Drosophila mechanosensory bristles from apoptosis by down-regulating the pro-apoptotic gene head involution defective. Both microRNAs are expressed in the bristle progenitors, and despite a difference in their seed sequence, they share this key common target. In miR-263a and miR-263b deletion mutants, loss of bristles appears to be sporadic, suggesting that the role of the microRNAs may be to ensure robustness of the patterning process by promoting survival of these functionally specified cells. In the context of the retina, this mechanism ensures that the interommatidial bristles are protected during the developmentally programmed wave of cell death that prunes excess cells in order to refine the pattern of the pupal retina.

  3. Drosophila microRNAs 263a/b confer robustness during development by protecting nascent sense organs from apoptosis.

    Directory of Open Access Journals (Sweden)

    Valérie Hilgers

    Full Text Available miR-263a/b are members of a conserved family of microRNAs that are expressed in peripheral sense organs across the animal kingdom. Here we present evidence that miR-263a and miR-263b play a role in protecting Drosophila mechanosensory bristles from apoptosis by down-regulating the pro-apoptotic gene head involution defective. Both microRNAs are expressed in the bristle progenitors, and despite a difference in their seed sequence, they share this key common target. In miR-263a and miR-263b deletion mutants, loss of bristles appears to be sporadic, suggesting that the role of the microRNAs may be to ensure robustness of the patterning process by promoting survival of these functionally specified cells. In the context of the retina, this mechanism ensures that the interommatidial bristles are protected during the developmentally programmed wave of cell death that prunes excess cells in order to refine the pattern of the pupal retina.

  4. Early somatosensory processing in individuals at risk for developing psychoses

    Directory of Open Access Journals (Sweden)

    Florence eHagenmuller

    2014-09-01

    Full Text Available Human cortical somatosensory evoked potentials (SEPs allow an accurate investigation of thalamocortical and early cortical processing. SEPs reveal a burst of superimposed early (N20 high-frequency oscillations around 600 Hz. Previous studies reported alterations of SEPs in patients with schizophrenia. This study addresses the question whether those alterations are also observable in populations at risk for developing schizophrenia or bipolar disorders. To our knowledge to date, this is the first study investigating SEPs in a population at risk for developing psychoses.Median nerve SEPs were investigated using multichannel EEG in individuals at risk for developing bipolar disorders (n=25, individuals with high-risk status (n= 59 and ultra-high-risk status for schizophrenia (n= 73 and a gender and age-matched control group (n=45. Strengths and latencies of low- and high-frequency components as estimated by dipole source analysis were compared between groups.Low- and high-frequency source activity was reduced in both groups at risk for schizophrenia, in comparison to the group at risk for bipolar disorders. HFO amplitudes were also significant reduced in subjects with high-risk status for schizophrenia compared to healthy controls. These differences were accentuated among cannabis non-users. Reduced N20 source strengths were related to higher positive symptom load.These results suggest that the risk for schizophrenia, in contrast to bipolar disorders, may involve an impairment of early cerebral somatosensory processing. Neurophysiologic alterations in schizophrenia precede the onset of initial psychotic episode and may serve as indicator of vulnerability for developing schizophrenia.

  5. Live cell imaging in Drosophila melanogaster.

    Science.gov (United States)

    Parton, Richard M; Vallés, Ana Maria; Dobbie, Ian M; Davis, Ilan

    2010-04-01

    Although many of the techniques of live cell imaging in Drosophila melanogaster are also used by the greater community of cell biologists working on other model systems, studying living fly tissues presents unique difficulties with regard to keeping the cells alive, introducing fluorescent probes, and imaging through thick, hazy cytoplasm. This article outlines the major tissue types amenable to study by time-lapse cinematography and different methods for keeping the cells alive. It describes various imaging and associated techniques best suited to following changes in the distribution of fluorescently labeled molecules in real time in these tissues. Imaging, in general, is a rapidly developing discipline, and recent advances in imaging technology are able to greatly extend what can be achieved with live cell imaging of Drosophila tissues. As far as possible, this article includes the latest technical developments and discusses likely future developments in imaging methods that could have an impact on research using Drosophila.

  6. Early growth and development of later life metabolic disorders.

    Science.gov (United States)

    Foo, Joo-Pin; Mantzoros, Christos

    2013-01-01

    Growth is effected via a complex interaction of genetic, nutritional, environmental and growth factors. Hormonal factors such as the growth hormone (GH) and insulin-like growth factor (IGF) signaling system, the human placental lactogen, and insulin play an integral role in early growth. Genetic factors affecting the GH-IGF system and insulin secretion and actions, and epigenetic mechanisms including DNA methylation have been further implicated as contributory factors. These hormonal systems, on a background of genetic susceptibility, together with other factors including maternal nutrition, placental and environmental factors, regulate not only early growth but also development. These interactions may impact on later health consequences in adult life. Accumulating data in the last few decades on developmental programming and later life metabolic disorders has provided a novel perspective on the possible pathogenesis of metabolic dysregulation. Despite postulations put forward to elucidate the mechanism underlying the association between early growth and later life metabolic disorders, it remains unclear what the dominant factor(s) would be, how any underlying mechanisms interact, or whether these mechanisms are truly causal.

  7. SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dawei Gou

    Full Text Available DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patterns are dynamic rather than static and change in a gene-specific fashion during development and in diseased cells. However, the factors and mechanisms involved in dynamic, postembryonic DNA methylation remain unclear. Methylation of lysine 9 in histone H3 (H3-K9 by members of the Su(var3-9 family of histone methyltransferases (HMTs triggers embryonic DNA methylation in Arthropods and Chordates. Here, we demonstrate that Drosophila SETDB1 (dSETDB1 can mediate DNA methylation and silencing of genes and retrotransposons. We found that dSETDB1 tri-methylates H3-K9 and binds methylated CpA motifs. Tri-methylation of H3-K9 by dSETDB1 mediates recruitment of DNA methyltransferase 2 (Dnmt2 and Su(var205, the Drosophila ortholog of mammalian "Heterochromatin Protein 1", to target genes for dSETDB1. By enlisting Dnmt2 and Su(var205, dSETDB1 triggers DNA methylation and silencing of genes and retrotransposons in Drosophila cells. DSETDB1 is involved in postembryonic DNA methylation and silencing of Rt1b{} retrotransposons and the tumor suppressor gene retinoblastoma family protein 1 (Rb in imaginal discs. Collectively, our findings implicate dSETDB1 in postembryonic DNA methylation, provide a model for silencing of the tumor suppressor Rb, and uncover a role for cell type-specific DNA methylation in Drosophila development.

  8. Correlated changes in life history traits in response to selection for faster pre-adult development in the fruit fly Drosophila melanogaster.

    Science.gov (United States)

    Yadav, Pankaj; Sharma, Vijay Kumar

    2014-02-15

    Insects including the fruit fly Drosophila melanogaster are under intense pressure to develop rapidly because they inhabit ephemeral habitats. We have previously shown that when selection for faster development was artificially imposed on D. melanogaster in the laboratory, reduction of pre-adult development time and shortening of the clock period occurs, suggesting a role for circadian clocks in the regulation of life history traits. Circadian clocks in D. melanogaster have also been implicated in the control of metabolic pathways, ageing processes, oxidative stress and defense responses to exogenous stressors. In order to rigorously examine correlations between pre-adult development time and other life history traits, we assayed pre-adult survivorship, starvation and desiccation resistance, body size and body weight, fecundity and adult lifespan in faster developing populations of D. melanogaster. The results revealed that selection for faster pre-adult development significantly reduced several adult fitness traits in the faster developing flies without affecting pre-adult survivorship. Although overall fecundity of faster developing flies was reduced, their egg output per unit body weight was significantly higher than that of controls, indicating that reduction in adult lifespan might be due to disproportionate investment in reproduction. Thus our results suggest that selection for faster pre-adult development in D. melanogaster yields flies with higher reproductive fitness. Because these flies also have shorter clock periods, our results can be taken to suggest that pre-adult development time and circadian clock period are correlated with various adult life history traits in D. melanogaster, implying that circadian clocks may have adaptive significance.

  9. Drosophila melanogaster as a model organism to study nanotoxicity.

    Science.gov (United States)

    Ong, Cynthia; Yung, Lin-Yue Lanry; Cai, Yu; Bay, Boon-Huat; Baeg, Gyeong-Hun

    2015-05-01

    Drosophila melanogaster has been used as an in vivo model organism for the study of genetics and development since 100 years ago. Recently, the fruit fly Drosophila was also developed as an in vivo model organism for toxicology studies, in particular, the field of nanotoxicity. The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited due to high operational cost and ethical objections. Hence, Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity. This review discusses the basic biology of Drosophila, the toxicity of nanomaterials, as well as how the Drosophila model can be used to study the toxicity of various types of nanomaterials.

  10. A gene expression atlas of early craniofacial development.

    Science.gov (United States)

    Brunskill, Eric W; Potter, Andrew S; Distasio, Andrew; Dexheimer, Phillip; Plassard, Andrew; Aronow, Bruce J; Potter, S Steven

    2014-07-15

    We present a gene expression atlas of early mouse craniofacial development. Laser capture microdissection (LCM) was used to isolate cells from the principal critical microregions, whose development, differentiation and signaling interactions are responsible for the construction of the mammalian face. At E8.5, as migrating neural crest cells begin to exit the neural fold/epidermal ectoderm boundary, we examined the cranial mesenchyme, composed of mixed neural crest and paraxial mesoderm cells, as well as cells from adjacent neuroepithelium. At E9.5 cells from the cranial mesenchyme, overlying olfactory placode/epidermal ectoderm, and underlying neuroepithelium, as well as the emerging mandibular and maxillary arches were sampled. At E10.5, as the facial prominences form, cells from the medial and lateral prominences, the olfactory pit, multiple discrete regions of underlying neuroepithelium, the mandibular and maxillary arches, including both their mesenchymal and ectodermal components, as well as Rathke's pouch, were similarly sampled and profiled using both microarray and RNA-seq technologies. Further, we performed single cell studies to better define the gene expression states of the early E8.5 pioneer neural crest cells and paraxial mesoderm. Taken together, and analyzable by a variety of biological network approaches, these data provide a complementing and cross validating resource capable of fueling discovery of novel compartment specific markers and signatures whose combinatorial interactions of transcription factors and growth factors/receptors are responsible for providing the master genetic blueprint for craniofacial development.

  11. Proteomic analysis of early seed development in Pinus massoniana L.

    Science.gov (United States)

    Zhen, Yan; Zhao, Zhen-Zhou; Zheng, Ren-Hua; Shi, Jisen

    2012-05-01

    Understanding seed development is important for large-scale propagation and germplasm conservation for the Masson pine. We undertook a proteomic analysis of Masson pine seeds during the early stages of embryogenesis. Two-dimensional difference gel electrophoresis (2D DIGE) was used to quantify the differences in protein expression during early seed development. Using electrospray ionization mass spectrometry/mass spectrometry, we identified proteins from 43 gel spots that had been excised from preparative "pick" gels. Proteins involved in carbon metabolism were identified and were predominantly expressed at higher levels during the cleavage polyembryony and columnar embryo stages. Functional annotation of one seed protein revealed it involvement in programmed cell death and translation of selective mRNAs, which may play an important role in subordinate embryo elimination and suspensor degeneration in polyembryonic seed gymnosperms. Other identified proteins were associated with protein folding, nitrogen metabolism, disease/defense response, and protein storage, synthesis and stabilization. The comprehensive protein expression profiles generated by this study will provide new insights into the complex developmental process of seed development in Masson pine.

  12. Understanding Substorms in the Magnetotail: Early Development and Recent Progress

    Institute of Scientific and Technical Information of China (English)

    A.Nishida

    2011-01-01

    This is a concise review of physics of the substorm in the magnetotail.It consists of two parts.The first part summarizes historical developments in the early days of the space age (1960-1975) when the basic concepts such as magnetotail and reconnection were established and the leading model of the substorm was introduced.The second part is an overview of the research conducted in recent years (1995-2010) when very significant advances have been achieved in understanding the substorm physics by virtue of several major satellites missions that addressed the magnetotail physics intensively.

  13. Comparison of early gestational development between natural and stimulated pregnancies

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Soon Ae; Ahn, M. O.; Yoon, T. K.; Cha, G. Y. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1990-12-15

    In order to assess the difference in growth and development between the stimulated and natural pregnancies, we compared the sonographic measurement of early embryos from the fifth to seventh gestational week, in terms of mean size of gestational sac, crown rump length, fetal heart rate and yolk sac size between 26 ovulation stimulated pregnancies and 38 natural pre gnancies. The two groups were compared by multiple regression analysis, The data suggest that there is attend that embryos smaller in stimulated pregnancies though significant statistical differences was not proved

  14. APECS: A Network for Polar Early Career Scientist Professional Development

    Science.gov (United States)

    Enderlin, E. M.

    2014-12-01

    The Association of Polar Early Career Researchers (APECS) is an international and interdisciplinary organization for undergraduate and graduate students, postdoctoral researchers, early faculty members, educators and others with interests in the polar regions, alpine regions and the wider Cryosphere. APECS is a scientific, non-profit organization with free individual membership that aims to stimulate research collaborations and develop effective future leaders in polar research, education, and outreach. APECS grew out of the 4th International Polar Year (2007-08), which emphasized the need to stimulate and nurture the next generation of scientists in order to improve the understanding and communication of the polar regions and its global connections. The APECS organizational structure includes a Council and an elected Executive Committee that are supported by a Directorate. These positions are open to all individual members through a democratic process. The APECS Directorate is funded by the Norwegian Research Council, the University of Tromsø and the Norwegian Polar Institute and is hosted by the University of Tromsø. Early career scientists benefit from a range of activities hosted/organized by APECS. Every year, numerous activities are run with partner organizations and in conjunction with major polar conferences and meetings. In-person and online panels and workshops focus on a range of topics, from developing field skills to applying for a job after graduate school. Career development webinars are hosted each fall and topical research webinars are hosted throughout the year and archived online (http://www.apecs.is). The APECS website also contains abundant information on polar news, upcoming conferences and meetings, and job postings for early career scientists. To better respond to members' needs, APECS has national/regional committees that are linked to the international overarching organization. Many of these committees organize regional meetings or

  15. Retinoic acid synthesis and functions in early embryonic development

    Directory of Open Access Journals (Sweden)

    Kam Richard Kin Ting

    2012-03-01

    Full Text Available Abstract Retinoic acid (RA is a morphogen derived from retinol (vitamin A that plays important roles in cell growth, differentiation, and organogenesis. The production of RA from retinol requires two consecutive enzymatic reactions catalyzed by different sets of dehydrogenases. The retinol is first oxidized into retinal, which is then oxidized into RA. The RA interacts with retinoic acid receptor (RAR and retinoic acid X receptor (RXR which then regulate the target gene expression. In this review, we have discussed the metabolism of RA and the important components of RA signaling pathway, and highlighted current understanding of the functions of RA during early embryonic development.

  16. The FHA domain determines Drosophila Chk2/Mnk localization to key mitotic structures and is essential for early embryonic DNA damage responses.

    Science.gov (United States)

    Takada, Saeko; Collins, Eric R; Kurahashi, Kayo

    2015-05-15

    DNA damage responses, including mitotic centrosome inactivation, cell-cycle delay in mitosis, and nuclear dropping from embryo cortex, maintain genome integrity in syncytial Drosophila embryos. A conserved signaling kinase, Chk2, known as Mnk/Loki, is essential for the responses. Here we demonstrate that functional EGFP-Mnk expressed from a transgene localizes to the nucleus, centrosomes, interkinetochore/centromere region, midbody, and pseudocleavage furrows without DNA damage and in addition forms numerous foci/aggregates on mitotic chromosomes upon DNA damage. We expressed EGFP-tagged Mnk deletion or point mutation variants and investigated domain functions of Mnk in vivo. A triple mutation in the phosphopeptide-binding site of the forkhead-associated (FHA) domain disrupted normal Mnk localization except to the nucleus. The mutation also disrupted Mnk foci formation on chromosomes upon DNA damage. FHA mutations and deletion of the SQ/TQ-cluster domain (SCD) abolished Mnk transphosphorylations and autophosphorylations, indicative of kinase activation after DNA damage. A potent NLS was found at the C-terminus, which is required for normal Mnk function. We propose that the FHA domain in Mnk plays essential dual functions in mediating embryonic DNA damage responses by means of its phosphopeptide-binding ability: activating Mnk in the nucleus upon DNA damage and recruiting Mnk to multiple subcellular structures independently of DNA damage.

  17. External control of the Drosophila melanogaster egg to imago development period by specific combinations of 3D low-frequency electric and magnetic fields.

    Science.gov (United States)

    Makarov, Vladimir I; Khmelinskii, Igor

    2016-01-01

    We report that the duration of the egg-to-imago development period of the Drosophila melanogaster, and the imago longevity, are both controllable by combinations of external 3-dimensional (3D) low-frequency electric and magnetic fields (LFEMFs). Both these periods may be reduced or increased by applying an appropriate configuration of external 3D LFEMFs. We report that the longevity of D. melanogaster imagoes correlates with the duration of the egg-to-imago development period of the respective eggs. We infer that metabolic processes in both eggs and imago are either accelerated (resulting in reduced time periods) or slowed down (resulting in increased time periods). We propose that external 3D LFEMFs induce electric currents in live systems as well as mechanical vibrations on sub-cell, whole-cell and cell-group levels. These external fields induce media polarization due to ionic motion and orientation of electric dipoles that could moderate the observed effects. We found that the longevity of D. melanogaster imagoes is affected by action of 3D LFEMFs on the respective eggs in the embryonic development period (EDP). We interpret this effect as resulting from changes in the regulation mechanism of metabolic processes in D. melanogaster eggs, inherited by the resulting imagoes. We also tested separate effects of either 3D electric or 3D magnetic fields, which were significantly weaker.

  18. Cullin-5 and cullin-2 play a role in the development of neuromuscular junction and the female germ line of Drosophila

    Indian Academy of Sciences (India)

    Champakali Ayyub

    2011-08-01

    Cullins confer substrate specificity to E3-ligases which are multi-protein complexes involved in ubiquitin-mediated protein degradation or modification. There are six cullin genes in Drosophila melanogaster. We have raised an antibody against Cul-5 and demonstrated that it expresses in neuronal and non-neuronal cells throughout development. In the embryonic tracheal system, Cul-5 is enriched at fusion sites together with E-Cadherin and Fasciclin III. Mutations of cul-5 do not affect tracheal development but do show defects in the organization of synaptic boutons at the larval neuromuscular junction where the protein is expressed in a subset of motoneuron terminals. Loss of function of another cullin gene ‘cul-2’ results in similar defects at the larval neuromuscular junction although cul-2;cul-5 double mutants do not show an enhanced phenotype. Both cul-2 and cul-5 mutants show similar aberrations in the development of female germ line. Our results suggest that both of these cullin proteins participate in similar developmental processes.

  19. Atg6/UVRAG/Vps34-Containing Lipid Kinase Complex Is Required for Receptor Downregulation through Endolysosomal Degradation and Epithelial Polarity during Drosophila Wing Development

    Directory of Open Access Journals (Sweden)

    Péter Lőrincz

    2014-01-01

    Full Text Available Atg6 (Beclin 1 in mammals is a core component of the Vps34 PI3K (III complex, which promotes multiple vesicle trafficking pathways. Atg6 and Vps34 form two distinct PI3K (III complexes in yeast and mammalian cells, either with Atg14 or with UVRAG. The functions of these two complexes are not entirely clear, as both Atg14 and UVRAG have been suggested to regulate both endocytosis and autophagy. In this study, we performed a microscopic analysis of UVRAG, Atg14, or Atg6 loss-of-function cells in the developing Drosophila wing. Both autophagy and endocytosis are seriously impaired and defective endolysosomes accumulate upon loss of Atg6. We show that Atg6 is required for the downregulation of Notch and Wingless signaling pathways; thus it is essential for normal wing development. Moreover, the loss of Atg6 impairs cell polarity. Atg14 depletion results in autophagy defects with no effect on endocytosis or cell polarity, while the silencing of UVRAG phenocopies all but the autophagy defect of Atg6 depleted cells. Thus, our results indicate that the UVRAG-containing PI3K (III complex is required for receptor downregulation through endolysosomal degradation and for the establishment of proper cell polarity in the developing wing, while the Atg14-containing complex is involved in autophagosome formation.

  20. Early developing celiac disease in children with cerebral palsy.

    Science.gov (United States)

    Stenberg, Reidun; Kaukinen, Katri; Bengtsson, Mats; Lindberg, Eva; Dahle, Charlotte

    2011-12-01

    We have reported on increased levels of antibodies against gliadin and/or transglutaminase 2 (TG2) in children with cerebral palsy (CP) but without having increased prevalence of celiac disease (CD). The aim of the present study was to evaluate whether these children have mucosal signs of early developing CD, human leukocyte antigen (HLA)-DQ2/DQ8, and antibodies against deamidated gliadin peptides (DGP). Stored blood samples from 16 children with CP were analyzed regarding HLA-DQ2/DQ8 and anti-DGP antibodies. HLA-DQ2/DQ8 were analyzed by polymerase chain reaction sequence-specific oligonucleotide probes. Anti-DGP antibodies were analyzed with enzyme-linked immunosorbent assay. Small-bowel biopsies from 15 of these children were available for immunohistochemistry regarding IgA colocalized with TG2, densities of α/β+ and γ/δ+ intraepithelial lymphocytes. Mucosal immunoglobulin A (IgA) deposits colocalized with TG2 were found in the small-bowel biopsy from 1 patient with serum IgA-class anti-TG2 antibodies, HLA-DQ2, and gastrointestinal complaints. Another 2 children had slightly increased numbers of mucosal α/β+ and/or γ/δ+ intraepithelial lymphocytes. In total, 10 of 16 children were HLA-DQ2 and/or DQ8-positive. Anti-DGP antibodies were detected in sera from 4 of 16 children. In the present study, 1 child with CP had IgA colocalizing with TG2 in the small-bowel mucosa, suggesting CD at an early stage. Although the majority of children with CP and elevated levels of CD-related seromarkers are HLA-DQ2 and/or DQ8-positive, they have neither classical nor early developing CD.

  1. Early Requestive Development in Consecutive Third Language Learning

    Science.gov (United States)

    Safont-Jorda, Maria-Pilar

    2011-01-01

    While research on early simultaneous bilingual acquisition is well-documented, studies on multiple language acquisition in early childhood are still needed. Existing studies have mainly focused on early simultaneous acquisition of three or more languages. Some attention has already been paid to early pragmatic differentiation and cross-linguistic…

  2. Early Requestive Development in Consecutive Third Language Learning

    Science.gov (United States)

    Safont-Jorda, Maria-Pilar

    2011-01-01

    While research on early simultaneous bilingual acquisition is well-documented, studies on multiple language acquisition in early childhood are still needed. Existing studies have mainly focused on early simultaneous acquisition of three or more languages. Some attention has already been paid to early pragmatic differentiation and cross-linguistic…

  3. Early Neurobehavioral Development of Mice Lacking Endogenous PACAP.

    Science.gov (United States)

    Farkas, Jozsef; Sandor, Balazs; Tamas, Andrea; Kiss, Peter; Hashimoto, Hitoshi; Nagy, Andras D; Fulop, Balazs D; Juhasz, Tamas; Manavalan, Sridharan; Reglodi, Dora

    2017-04-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide. In addition to its diverse physiological roles, PACAP has important functions in the embryonic development of various tissues, and it is also considered as a trophic factor during development and in the case of neuronal injuries. Data suggest that the development of the nervous system is severely affected by the lack of endogenous PACAP. Short-term neurofunctional outcome correlates with long-term functional deficits; however, the early neurobehavioral development of PACAP-deficient mice has not yet been evaluated. Therefore, the aim of the present study was to describe the postnatal development of physical signs and neurological reflexes in mice partially or completely lacking PACAP. We examined developmental hallmarks during the first 3 weeks of the postnatal period, during which period most neurological reflexes and motor coordination show most intensive development, and we describe the neurobehavioral development using a complex battery of tests. In the present study, we found that PACAP-deficient mice had slower weight gain throughout the observation period. Interestingly, mice partially lacking PACAP weighed significantly less than homozygous mice. There was no difference between male and female mice during the first 3 weeks. Some other signs were also more severely affected in the heterozygous mice than in the homozygous mice, such as air righting, grasp, and gait initiation reflexes. Interestingly, incisor teeth erupted earlier in mice lacking PACAP. Motor coordination, shown by the number of foot-faults on an elevated grid, was also less developed in PACAP-deficient mice. In summary, our results show that mice lacking endogenous PACAP have slower weight gain during the first weeks of development and slower neurobehavioral development regarding a few developmental hallmarks.

  4. Early lexical development in Spanish-speaking infants and toddlers.

    Science.gov (United States)

    Jackson-Maldonado, D; Thal, D; Marchman, V; Bates, E; Gutierrez-Clellen, V

    1993-10-01

    This paper describes the early lexical development of a group of 328 normal Spanish-speaking children aged 0;8 to 2;7. First the development and structure of a new parent report instrument, Inventario del Desarollo de Habilidades Communicativas is described. Then five studies carried out with the instrument are presented. In the first study vocabulary development of Spanish-speaking infants and toddlers is compared to that of English-speaking infants and toddlers. The English data were gathered using a comparable parental report, the MacArthur Communicative Development Inventories. In the second study the general characteristics of Spanish language acquisition, and the effects of various demographic factors on that process, are examined. Study 3 examines the differential effects of three methods of collecting the data (mail-in, personal interview, and clinic waiting room administration). Studies 4 and 5 document the reliability and validity of the instrument. Results show that the trajectories of development are very similar for Spanish- and English-speaking children in this age range, that children from varying social groups develop similarly, and that mail-in and personal interview administration techniques produce comparable results. Inventories administered in a medical clinic waiting room, on the other hand, produced lower estimates of toddler vocabulary than the other two models.

  5. [Development and the developmental disorders of human brain. I. Early development of the cerebrum

    NARCIS (Netherlands)

    Donkelaar, H.J. ten; Wesseling, P.; Lammens, M.M.Y.; Renier, W.O.; Mullaart, R.A.; Thijssen, H.O.M.

    2001-01-01

    The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early

  6. Early Development of the Gut Microbiota and Immune Health

    Directory of Open Access Journals (Sweden)

    M. Pilar Francino

    2014-09-01

    Full Text Available In recent years, the increase in human microbiome research brought about by the rapidly evolving “omic” technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the ‘early programming hypothesis’, according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gut microbiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction.

  7. Development of children’s early understanding of numeric structure

    Directory of Open Access Journals (Sweden)

    Vasilyeva, Marina

    2016-09-01

    Full Text Available Understanding of the base-10 structure of multi-digit numbers is one of the critical aspects in early mathematics learning. It has been documented that children from different countries vary in their use of base-10 representations. Questions concerning potential sources of this variability have been debated for decades. One commonly posited explanation is that some languages provide explicit cues about the structure of multi-digit numbers, facilitating the development of base-10 representations. In the present study, we tested this view against an alternative view, positing that variability in children’s learning of numeric structure may reflect differences in their experiences with numbers. The study examined kindergartners and first-graders from four countries: Taiwan, South Korea, the USA, and Russia. Results showed that the use of base-10 representations by American first-graders increased dramatically over the last decades, following changes in curricular guidelines. First-graders across the four countries showed some differences in performance (however, not consistent with the language account, whereas kindergartners performed comparably despite the differences in their languages. The results suggest that the nature of early math instruction may be critical for children’s developing understanding of numeric structure.

  8. Dihydroartemisinin promotes angiogenesis during the early embryonic development of zebrafish

    Institute of Scientific and Technical Information of China (English)

    Qian BA; Juan DUAN; Jia-qiang TIAN; Zi-liang WANG; Tao CHEN; Xiao-guang LI; Pei-zhan CHEN

    2013-01-01

    Aim:To investigate the embryotoxicity of dihydroartemisinin (DHA),the main active metabolite of artemisinin,in zebrafish,and explore the corresponding mechanisms.Methods:The embryos of wild type and TG (flk1:GFP) transgenic zebrafish were exposed to DHA.Developmental phenotypes of the embryos were observed.Development of blood vessels was directly observed in living embryos of TG (flk1:GFP) transgenic zebrafish under fluorescence microscope.The expression of angiogenesis marker genes vegfa,flk1,and flt1 in the embryos was detected using real-time PCR and RNA in situ hybridization assays.Results:Exposure to DHA (1-10 mg/L) dose-dependently caused abnormal zebrafish embryonic phenotypes in the early developmental stage.Furthermore,exposure to DHA (10 mg/L) resulted in more pronounced embryonic angiogenesis in TG (flk1:GFP)zebrafish line.Exposure to DHA (10 mg/L) significantly increased the mRNA expression of vegfa,flk1,and flt1 in the embryos.Knockdown of the ilk1 protein partially blocked the effects of DHA on embryogenesis.Conclusion:DHA causes abnormal embryonic phenotypes and promotes angiogenesis in zebrafish early embryonic development,demonstrating the potential embryotoxicity of DHA.

  9. Adult Neurogenesis in Drosophila

    OpenAIRE

    Ismael Fernández-Hernández; Christa Rhiner; Eduardo Moreno

    2013-01-01

    Adult neurogenesis has been linked to several cognitive functions and neurological disorders. Description of adult neurogenesis in a model organism like Drosophila could facilitate the genetic study of normal and abnormal neurogenesis in the adult brain. So far, formation of new neurons has not been detected in adult fly brains and hence has been thought to be absent in Drosophila. Here, we used an improved lineage-labeling method to show that, surprisingly, adult neurogenesis occurs in the m...

  10. Early Vocabulary Development of Australian Indigenous Children: Identifying Strengths

    Directory of Open Access Journals (Sweden)

    Brad M. Farrant

    2014-01-01

    Full Text Available The current study sought to increase our understanding of the factors involved in the early vocabulary development of Australian Indigenous children. Data from the Longitudinal Study of Indigenous Children were available for 573 Indigenous children (291 boys who spoke English (M=37.0 months, SD=5.4 months, at wave 3. Data were also available for 86 children (51 boys who spoke an Indigenous language (M=37.1 months, SD=6.0 months, at wave 3. As hypothesised, higher levels of parent-child book reading and having more children’s books in the home were associated with better English vocabulary development. Oral storytelling in Indigenous language was a significant predictor of the size of children’s Indigenous vocabulary.

  11. Language, bilingualism, and executive functioning in early development.

    Science.gov (United States)

    Morton, J Bruce

    2010-12-01

    Okanda, et al. (2010) reported new evidence concerning associations between language ability, bilingualism, and executive functioning early in development. The paper adds to a growing body of literature suggesting that bilingualism is associated with advantages in executive functioning generally, and the Dimensional Change Card Sort task in particular. However, as with all findings that hinge on between-group comparisons, there is a need to exercise caution before drawing firm conclusions about the effects of bilingualism on the development of executive control. Several lines of recent evidence are outlined that challenge key assumptions underlying the standard account of the bilingual advantage. Okanda, et al.'s findings are discussed in light of this evidence.

  12. Modeling and managing risk early in software development

    Science.gov (United States)

    Briand, Lionel C.; Thomas, William M.; Hetmanski, Christopher J.

    1993-01-01

    In order to improve the quality of the software development process, we need to be able to build empirical multivariate models based on data collectable early in the software process. These models need to be both useful for prediction and easy to interpret, so that remedial actions may be taken in order to control and optimize the development process. We present an automated modeling technique which can be used as an alternative to regression techniques. We show how it can be used to facilitate the identification and aid the interpretation of the significant trends which characterize 'high risk' components in several Ada systems. Finally, we evaluate the effectiveness of our technique based on a comparison with logistic regression based models.

  13. The hnRNP A1 homolog Hrp36 is essential for normal development, female fecundity, omega speckle formation and stress tolerance in Drosophila melanogaster

    Indian Academy of Sciences (India)

    Anand K Singh; Subhash C Lakhotia

    2012-12-01

    Hrp36/Hrb87F is one of the most abundant and well-characterized hnRNP A homolog in Drosophila and is shown to have roles in regulation of alternative splicing, heterochromatin formation, neurodegeneration, etc. Yet, hrp36 null individuals were reported to be viable and without any apparent phenotype, presumably because of overlapping functions provided by Hrp38 and related proteins. Here we show that loss of both copies of hrp36 gene slows down development with significant reduction in adult life span, decreased female fecundity and high sensitivity to starvation and thermal stresses. In the absence of Hrp36, the nucleoplasmic omega speckles are nearly completely disrupted. The levels of nuclear matrix protein Megator and the chromatin remodeller ISWI are significantly elevated in principal cells of larval Malpighian tubules, which also display additional endoreplication cycles and good polytene chromosomes. We suggest that besides the non-coding hsr-n transcripts, the Hrp36 protein is also a core constituent of omega speckles. The heat-shock-induced association of other hnRNPs at the hsr locus is affected in hrp36 null cells, which may be one of the reasons for their high sensitivity to cell stress. Therefore, in spite of the functional redundancy provided by Hrp38, Hrp36 is essential for normal development and for survival under conditions of stress.

  14. Characterization of big bang, a novel gene encoding for PDZ domain-containing proteins that are dynamically expressed throughout Drosophila development.

    Science.gov (United States)

    Kim, Sabrina Y; Renihan, Maia K; Boulianne, Gabrielle L

    2006-06-01

    PDZ (PSD-95, Discs-large, ZO-1) domain proteins often function as scaffolding proteins and have been shown to play important roles in diverse cellular processes such as the establishment and maintenance of cell polarity, and signal transduction. Here, we report the identification and cloning of a novel Drosophila melanogaster gene that is predicted to produce several different PDZ domain-containing proteins through alternative promoter usage and alternative splicing. This gene, that we have named big bang (bbg), was first identified as C96-GAL4, a GAL4 enhancer trap line that was generated in our lab. To further characterize bbg, its expression pattern was examined in ovaries, embryos, and late third instar larvae using UAS reporter gene constructs, in situ hybridization, or immunocytochemistry. In addition, the expression of alternatively spliced transcripts was examined in more detail using in situ hybridization. We find that during embryogenesis bbg is predominantly expressed in the developing gut, but it is also expressed in external sensory organs found in the epidermis. In the late third instar larva, bbg is expressed along the presumptive wing margin in the wing disc, broadly in the eye disc, and in other imaginal discs as well as in the brain. The expression patterns observed are dynamic and specific during development, suggesting that like other genes that encode for several different PDZ domain protein isoforms, bbg likely plays important roles in multiple developmental processes.

  15. The hnRNP A1 homolog Hrp36 is essential for normal development, female fecundity, omega speckle formation and stress tolerance in Drosophila melanogaster

    Indian Academy of Sciences (India)

    Anand K Singh; Subhash C Lakhotia

    2012-09-01

    Hrp36/Hrb87F is one of the most abundant and well-characterized hnRNP A homolog in Drosophila and is shown to have roles in regulation of alternative splicing, heterochromatin formation, neurodegeneration, etc. Yet, hrp36 null individuals were reported to be viable and without any apparent phenotype, presumably because of overlapping functions provided by Hrp38 and related proteins. Here we show that loss of both copies of hrp36 gene slows down development with significant reduction in adult life span, decreased female fecundity and high sensitivity to starvation and thermal stresses. In the absence of Hrp36, the nucleoplasmic omega speckles are nearly completely disrupted. The levels of nuclear matrix protein Megator and the chromatin remodeller ISWI are significantly elevated in principal cells of larval Malpighian tubules, which also display additional endoreplication cycles and good polytene chromosomes. We suggest that besides the non-coding hsr-n transcripts, the Hrp36 protein is also a core constituent of omega speckles. The heat-shock-induced association of other hnRNPs at the hsr locus is affected in hrp36 null cells, which may be one of the reasons for their high sensitivity to cell stress. Therefore, in spite of the functional redundancy provided by Hrp38, Hrp36 is essential for normal development and for survival under conditions of stress.

  16. KIF27 is one of orthologs for Drosophila Costal-2.

    Science.gov (United States)

    Katoh, Yuriko; Katoh, Masaru

    2004-12-01

    Signals of Hedgehog family proteins (SHH, IHH and DHH) are transduced through Patched family receptors (PTCH1 and PTCH2) and Smoothened (SMO) to GLI family transcription factors (GLI1, GLI2 and GLI3). SHH plays a key role in development and progression of pancreatic cancer, gastric cancer, basal cell carcinoma, and brain tumors. Drosophila Costal-2 (Cos2) is implicated in the Hedgehog pathway through the interaction with Smoothened (Smo), Cubitus interruptus (Ci), Fused (Fu), and microtubule; however, mammalian ortholog of Drosophila Cos2 remained to be identified. Here we identified and characterized human ortholog of Drosophila Cos2 by using bioinformatics. Full-length Drosophila Cos2 was most homologous to human KIF27, followed by mouse Kif7, and other KIF family members. KIF27 gene at human chromosome 9q22.1 and KIF7 gene at human chromosome 15q26.1 were paralogs within the human genome. Phylogenetic analysis revealed that KIF27, Kif7, KIF4A, KIF4B and KIF21A constitute the KIF27 subfamily among mammalian Kinesin family. Drosophila Cos2 protein consists of Kinesin motor (KISc) domain, Ci-binding domain, and Smo-binding domain. KIF27 itself shared the common domain structure with Drosophila Cos2, while other members of KIF27 subfamily shared partial domain structure with Drosophila Cos2. These facts indicate that KIF27 is one of mammalian orthologs for Drosophila Cos2.

  17. Dual effects of fluoxetine on mouse early embryonic development

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang-Woon [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of); Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University, Changwon 630-723 (Korea, Republic of); Choe, Changyong [National Institute of Animal Science, RDA, Cheonan 330-801 (Korea, Republic of); Kim, Eun-Jin [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of); Lee, Jae-Ik [Department of Obstetrics and Gynecology, Gyeongsang National University Hospital, Jinju 660-702 (Korea, Republic of); Yoon, Sook-Young [Fertility Center of CHA Gangnam Medical Center, CHA University, Seoul 135-081 (Korea, Republic of); Cho, Young-Woo; Han, Sunkyu; Tak, Hyun-Min; Han, Jaehee [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of); Kang, Dawon, E-mail: dawon@gnu.ac.kr [Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751 (Korea, Republic of)

    2012-11-15

    Fluoxetine, a selective serotonin reuptake inhibitor, regulates a variety of physiological processes, such as cell proliferation and apoptosis, in mammalian cells. Little is known about the role of fluoxetine in early embryonic development. This study was undertaken to investigate the effect of fluoxetine during mouse early embryonic development. Late two-cell stage embryos (2-cells) were cultured in the presence of various concentrations of fluoxetine (1 to 50 μM) for different durations. When late 2-cells were incubated with 5 μM fluoxetine for 6 h, the percentage that developed into blastocysts increased compared to the control value. However, late 2-cells exposed to fluoxetine (5 μM) over 24 h showed a reduction in blastocyst formation. The addition of fluoxetine (5 μM) together with KN93 or KN62 (calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors) failed to increase blastocyst formation. Fluoxetine treatment inhibited TREK-1 and TREK-2, members of the two-pore domain K{sup +} channel family expressed in mouse embryos, activities, indicating that fluoxetine-induced membrane depolarization in late 2-cells might have resulted from TREK inhibition. In addition, long-term exposure to fluoxetine altered the TREK mRNA expression levels. Furthermore, injection of siRNA targeting TREKs significantly decreased blastocyst formation by ∼ 30% compared to injection of scrambled siRNA. Long-term exposure of fluoxetine had no effect on blastocyst formation of TREK deficient embryos. These results indicate that low-dose and short-term exposures of late 2-cells to fluoxetine probably increase blastocyst formation through activation of CaMKII-dependent signal transduction pathways, whereas long-term exposure decreases mouse early embryonic development through inhibition of TREK channel gating. Highlights: ► Short-term exposure of 2-cells to fluoxetine enhances mouse blastocyst formation. ► The enhancive effect of fluoxetine is resulted from Ca

  18. Early intestinal Bacteroides fragilis colonisation and development of asthma

    Directory of Open Access Journals (Sweden)

    Goossens Herman

    2008-09-01

    Full Text Available Abstract Background The 'hygiene hypothesis' suggests that early exposure to microbes can be protective against atopic disease. The intestinal microbial flora could operate as an important postnatal regulator of the Th1/Th2 balance. The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life. Methods In a prospective birth cohort, 117 children were classified according to the Asthma Predictive Index. A positive index included wheezing during the first three years of life combined with eczema in the child in the first years of life or with a parental history of asthma. A faecal sample was taken at the age of 3 weeks and cultured on selective media. Results Asthma Predictive Index was positive in 26/117 (22% of the children. The prevalence of colonisation with Bacteroides fragilis was higher at 3 weeks in index+ compared to index- children (64% vs. 34% p Bacteroides fragilis and Total Anaerobes counts at 3 weeks were significantly higher in children with a positive index as compared with those without. After adjusting for confounders a positive association was found between Bacteroides fragilis colonisation and Asthma Predictive Index (odds ratio: 4,4; confidence interval: 1,7 – 11,8. Conclusion Bacteroides fragilis colonisation at age 3 weeks is an early indicator of possible asthma later in life. This study could provide the means for more accurate targeting of treatment and prevention and thus more effective and better controlled modulation of the microbial milieu.

  19. Macrosomia has its roots in early placental development.

    Science.gov (United States)

    Schwartz, N; Quant, H S; Sammel, M D; Parry, S

    2014-09-01

    We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant. We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11-14 weeks and 18-24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 g) and LGA (birth weight ≥90th percentile). The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71-0.77). Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Ni^2+、Hg^2+对果蝇生长发育的影响%The Effects of Ni2+ and Hg2+ on the Growth and Development of Drosophila Melanogaster

    Institute of Scientific and Technical Information of China (English)

    曾秀存

    2012-01-01

    Drosophila melanogasters were cultured in the media with the different concentrations of nickelous nitrate and the mercuric chloride (0.5μg/mL, 5μ/mL, 151μg/mL, 301a, g/mL). The effect of nickelous nitrate and the mercuric chloride on its Male-female sex ratio of adults insect, survival rate of adult insect, the weight of adult insect. The results showed that with nickel, mercury concentration and generation of extended treatment, nickel ions on the Drosophila male and female sex ratio, survival rate and weight were less than mercury ions; High concentrations of mercury ions significantly reduce the development of male Drosophila melanogaster, reduce the survival rate of Drosophila, and restrain weight gain of Drosophila; Mercury ions cause severer injury on compared with nickel ions. Drosophila,%以黑体红眼长翅果蝇(Drosophilamelanogaster)为材料,培养基用硝酸镍和氯化汞染毒(浓度为0.5μg/mL、51MmL、151a,g/mL、30μg/mL)后对果蝇后代的雌雄性比、存活率,体重的影响进行研究.结果表明:随着镍、汞浓度的增加和处理世代的增加,Ni^2+对果蝇雌雄性比、存活率和体重的毒害较Hg^2+轻;高浓度的Hg^2+严重抑制雄果蝇的发育;降低果蝇的存活率,抑制果蝇体重的增加.这表明Hg^2+对果蝇的毒害要比Ni“重.

  1. Symmetry breaking and convergent extension in early chordate development.

    Science.gov (United States)

    Schiffmann, Yoram

    2006-10-01

    The initiation of axis, polarity, cell differentiation, and gastrulation in the very early chordate development is due to the breaking of radial symmetry. It is believed that this occurs by an external signal. We suggest instead spontaneous symmetry breaking through the agency of the Turing-Child field. Increased size or decreased diffusivity, both brought about by mitotic activity, cause the spontaneous loss of stability of the homogeneous state and the evolution of the metabolic pattern during development. The polar metabolic pattern is the cause of polar gene expression, polar morphogenesis (gastrulation), and polar mitotic activity. The Turing-Child theory explains not only the spontaneous formation of the invagination in gastrulation but also the coherent cell movement observed in convergence and extension during gastrulation and neurulation. The theory is demonstrated with respect to experimental observations on the early development of fish, amphibian, and the chick. The theory can explain a multitude of experimental details. For example, it explains the splayed polar progression of reduction in the fish blastoderm. Reduction starts on that side of the blastoderm margin, which will initiate invagination several hours later. It progresses toward the blastoderm center and somewhat laterally from this future "dorsal lip". This is precisely as predicted by a Turing-Child system in a circle. And for a fish like zebrafish with a blastoderm that is slightly oval, reduction is observed to progress along the long axis of the ellipse, which is what Turing-Child theory predicts. In general the shape and the chemical nature of the experimental patterns are the same as predicted by the Turing couple (cAMP, ATP). Embryological polarity and convergent extension are based on polar eigenfunction and saddle-shaped eigenfunction, respectively.

  2. Tip cell-derived RTK signaling initiates cell movements in the Drosophila stomatogastric nervous system anlage.

    Science.gov (United States)

    González-Gaitán, M; Jäckle, H

    2000-10-01

    The stomatogastric nervous system (SNS) of Drosophila is a simply organized neural circuitry that innervates the anterior enteric system. Unlike the central and the peripheral nervous systems, the SNS derives from a compact epithelial anlage in which three invagination centers, each giving rise to an invagination fold headed by a tip cell, are generated. Tip cell selection involves lateral inhibition, a process in which Wingless (Wg) activity adjusts the range of Notch signaling. Here we show that RTK signaling mediated by the Drosophila homolog of the epidermal growth factor receptor, DER, plays a key role in two consecutive steps during early SNS development. Like Wg, DER signaling participates in adjusting the range of Notch-dependent lateral inhibition during tip cell selection. Subsequently, tip cells secrete the DER ligand Spitz and trigger local RTK signaling, which initiates morphogenetic movements resulting in the tip cell-directed invaginations within the SNS anlage.

  3. Longitudinal development of prefrontal function during early childhood.

    Science.gov (United States)

    Moriguchi, Yusuke; Hiraki, Kazuo

    2011-04-01

    This is a longitudinal study on development of prefrontal function in young children. Prefrontal areas have been observed to develop dramatically during early childhood. To elucidate this development, we gave children cognitive shifting tasks related to prefrontal function at 3 years of age (Time 1) and 4 years of age (Time 2). We then monitored developmental changes in behavioral performance and examined prefrontal activation using near infrared spectroscopy. We found that children showed better behavioral performance and significantly stronger inferior prefrontal activation at Time 2 than they did at Time 1. Moreover, we demonstrated individual differences in prefrontal activation for the same behavioral tasks. Children who performed better in tasks at Time 1 showed significant activation of the right inferior prefrontal regions at Time 1 and significant activation of the bilateral inferior prefrontal regions at Time 2. Children who showed poorer performance at Time 1 exhibited no significant inferior prefrontal activation at Time 1 but significant left inferior prefrontal activation at Time 2. These results indicate the importance of the longitudinal method to address the link between cognitive and neural development.

  4. Mechanical origins of rightward torsion in early chick brain development

    Science.gov (United States)

    Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

    2015-03-01

    During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

  5. Transcriptome Analysis of Drosophila melanogaster Third Instar Larval Ring Glands Points to Novel Functions and Uncovers a Cytochrome p450 Required for Development

    Science.gov (United States)

    Christesen, Danielle; Yang, Ying Ting; Somers, Jason; Robin, Charles; Sztal, Tamar; Batterham, Philip; Perry, Trent

    2016-01-01

    In Drosophila melanogaster larvae, the ring gland (RG) is a control center that orchestrates major developmental transitions. It is a composite organ, consisting of the prothoracic gland, the corpus allatum, and the corpora cardiaca, each of which synthesizes and secretes a different hormone. Until now, the RG’s broader developmental roles beyond endocrine secretion have not been explored. RNA sequencing and analysis of a new transcriptome resource from D. melanogaster wandering third instar larval RGs has provided a fascinating insight into the diversity of developmental signaling in this organ. We have found strong enrichment of expression of two gene pathways not previously associated with the RG: immune response and fatty acid metabolism. We have also uncovered strong expression for many uncharacterized genes. Additionally, RNA interference against RG-enriched cytochrome p450s Cyp6u1 and Cyp6g2 produced a lethal ecdysone deficiency and a juvenile hormone deficiency, respectively, flagging a critical role for these genes in hormone synthesis. This transcriptome provides a valuable new resource for investigation of roles played by the RG in governing insect development. PMID:27974438

  6. The role of the effector caspases drICE and dcp-1 for cell death and corpse clearance in the developing optic lobe in Drosophila.

    Science.gov (United States)

    Akagawa, Hiromi; Hara, Yusuke; Togane, Yu; Iwabuchi, Kikuo; Hiraoka, Tsuyoshi; Tsujimura, Hidenobu

    2015-08-15

    In the developing Drosophila optic lobe, cell death occurs via apoptosis and in a distinctive spatio-temporal pattern of dying cell clusters. We analyzed the role of effector caspases drICE and dcp-1 in optic lobe cell death and subsequent corpse clearance using mutants. Neurons in many clusters required either drICE or dcp-1 and each one is sufficient. This suggests that drICE and dcp-1 function in cell death redundantly. However, dying neurons in a few clusters strictly required drICE but not dcp-1, but required drICE and dcp-1 when drICE activity was reduced via hypomorphic mutation. In addition, analysis of the mutants suggests an important role of effecter caspases in corpse clearance. In both null and hypomorphic drICE mutants, greater number of TUNEL-positive cells were observed than in wild type, and many TUNEL-positive cells remained until later stages. Lysotracker staining showed that there was a defect in corpse clearance in these mutants. All the results suggested that drICE plays an important role in activating corpse clearance in dying cells, and that an additional function of effector caspases is required for the activation of corpse clearance as well as that for carrying out cell death.

  7. New functions of the Drosophila rhomboid gene during embryonic and adult development are revealed by a novel genetic method, enhancer piracy.

    Science.gov (United States)

    Noll, R; Sturtevant, M A; Gollapudi, R R; Bier, E

    1994-08-01

    Localized expression of the Drosophila rhomboid (rho) gene has been proposed to hyperactivate EGF-Receptor signaling in specific cells during development of the embryo and adult. In this report we use a novel transposon based genetic method, enhancer piracy, to drive ectopic expression of a rho cDNA transgene by endogenous genomic enhancers. Many enhancer piracy transposon-rho insertions cause dominant phenotypes, over half of which cannot be duplicated by ubiquitous expression of rho. Genetic interactions between various dominant enhancer piracy alleles and mutations in the EGF-R/RAS signaling pathway indicate that many of these novel phenotypes result from ectopic activation of EGF-R signaling. Patterned mis-expression of the rho cDNA transgene correlates in several cases with localized dominant enhancer piracy phenotypes. Enhancer piracy lines reveal an unanticipated role for rho in imaginal disc formation and provide the first evidence that mis-expression of rho is sufficient for converting entire intervein sectors into veins. Enhancer piracy may prove to be a general strategy for obtaining dominant alleles of a gene of interest in diverse insects, worms, plants, and potentially in vertebrates such as mice and fish.

  8. chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation and stem cell self-renewal in Drosophila

    Science.gov (United States)

    Flaherty, Maria Sol; Salis, Pauline; Evans, Cory J.; Ekas, Laura A.; Marouf, Amine; Zavadil, Jiri; Banerjee, Utpal; Bach, Erika A.

    2010-01-01

    SUMMARY The Drosophila STAT transcription factor Stat92E regulates diverse functions, including organ development and stem cell self-renewal. However, the Stat92E functional effectors that mediate these processes are largely unknown. Here we show that chinmo is a cell-autonomous, downstream mediator of Stat92E that shares numerous functions with this protein. Loss of either gene results in malformed eyes and head capsules due to defects in eye progenitor cells. Hyperactivation of Stat92E or misexpression of Chinmo results in blood cell tumors. Both proteins are expressed in germline (GSCs) and cyst stem cells (CySCs) in the testis. While Stat92E is required for the self-renewal of both populations, chinmo is only required in CySCs, indicating that Stat92E regulates self-renewal in different stem cells through independent effectors. Like hyperactivated Stat92E, Chinmo misexpression in CySCs is sufficient to maintain GSCs non-autonomously. Chinmo is therefore a key effector of JAK/STAT signaling in a variety of developmental and pathological contexts. PMID:20412771

  9. Functional characterization of the Drosophila MRP (mitochondrial RNA processing) RNA gene.

    Science.gov (United States)

    Schneider, Mary D; Bains, Anupinder K; Rajendra, T K; Dominski, Zbigniew; Matera, A Gregory; Simmonds, Andrew J

    2010-11-01

    MRP RNA is a noncoding RNA component of RNase mitochondrial RNA processing (MRP), a multi-protein eukaryotic endoribonuclease reported to function in multiple cellular processes, including ribosomal RNA processing, mitochondrial DNA replication, and cell cycle regulation. A recent study predicted a potential Drosophila ortholog of MRP RNA (CR33682) by computer-based genome analysis. We have confirmed the expression of this gene and characterized the phenotype associated with this locus. Flies with mutations that specifically affect MRP RNA show defects in growth and development that begin in the early larval period and end in larval death during the second instar stage. We present several lines of evidence demonstrating a role for Drosophila MRP RNA in rRNA processing. The nuclear fraction of Drosophila MRP RNA localizes to the nucleolus. Further, a mutant strain shows defects in rRNA processing that include a defect in 5.8S rRNA processing, typical of MRP RNA mutants in other species, as well as defects in early stages of rRNA processing.

  10. Recent psychological explanations of infant development and scales of early mental development

    Directory of Open Access Journals (Sweden)

    Maja Zupančič

    2002-12-01

    Full Text Available This paper reviews early infant measures based on standardised scales of development – both traditional ones and those based on Piaget's sensory-motor theory – and assesses their validity in predicting later mental development. The extremely low predictive power of test scores based on these measures in infancy has provided additional support for discontinuity theories of mental development from infancy to childhood. Conversely, the constructs implicit in earlier measures have been thoroughly criticised, and the search for valid measures of infant development that would reflect a construct similar to mental abilities in childhood has begun. At the outset, research was mostly influenced by the information processing theory. Two broad measures of information processing have been shown to be the most relevant indicators of an infant's mental development, namely habituation and dishabituation. Recent mental scales, such as the Bayley Scales of Infant Development-II, thus include items that measure the efficiency of an infant's information processing. Examples of such items are presented and interpreted, as are items reflecting the development of object permanence, the only early sensory-motor measure that shows better predictive effectiveness when compared to traditional developmental test scores. Several newly-developed indicators of infants' mental development, which utilize other measures than those derived from the information-processing approach, are surveyed (understanding causal relations, joint attention behaviours, representation of number, and their possible application within the context of potential items for early mental scales is discussed. Finally, the Bayley Scales of Infant Development-II, currently one of the best measures of early development, and presently undergoing a standardisation procedure in Slovenia, is evaluated, with analyses of some items from the Mental scale presented within the text.

  11. ATLIS. Early Childhood Development and the Electronic Age.

    Science.gov (United States)

    Alexander, Nancy P.

    1994-01-01

    Describes the America Tomorrow Leadership Information Service (ATLIS) and how this information can benefit early childhood professionals. Discusses the future of telecommunications in the early childhood profession and includes a glossary of telecommunications terms. (HTH)

  12. Nuclear lamins during gametogenesis, fertilization and early development

    Science.gov (United States)

    Maul, G. G.; Schatten, G.

    1986-01-01

    The distribution of lamins (described by Gerace, 1978, as major proteins of nuclear envelope) during gametogenesis, fertilization, and early development was investigated in germ cells of a mouse (Mus musculus), an echinoderm (Lytechinus variegatus), and the surf clam (Spisula solidissima) was investigated in order to determine whether the differences detected could be correlated with differences in the function of cells in these stages of the germ cells. In order to monitor the behavior of lamins, the gametes and embryos were labeled with antibodies to lamins A, C, and B extracted from autoimmune sera of patients with scleroderma and Lupus erythematosus. Results indicated that lamin B could be identified in nuclear envelopes on only those nuclei where chromatin is attached and where RNA synthesis takes place.

  13. From universal to language-specific in early grammatical development.

    Science.gov (United States)

    Bowerman, M

    1994-10-29

    Attempts to explain children's grammatical development often assume a close initial match between units of meaning and units of form; for example, agents are said to map to sentence-subjects and actions to verbs. The meanings themselves, according to this view, are not influenced by language, but reflect children's universal non-linguistic way of understanding the world. This paper argues that, contrary to this position, meaning as it is expressed in children's early sentences is, from the beginning, organized on the basis of experience with the grammar and lexicon of a particular language. As a case in point, children learning English and Korean are shown to express meanings having to do with direct motion according to language-specific principles of semantic and grammatical structuring from the earliest stages of word combination.

  14. Women, "Star Trek," and the early development of fannish vidding

    Directory of Open Access Journals (Sweden)

    Francesca Coppa

    2008-09-01

    Full Text Available This paper argues that the practices and aesthetics of vidding were structured by the relationship of Star Trek's female fans to that particular televisual text. Star Trek fandom was the crucible within which vidding developed because Star Trek's narrative impelled female fans to take on two positions often framed as contradictory in mainstream culture: the desiring body, and the controlling voice of technology. To make a vid, to edit footage to subtext-revealing music, is to unite these positions: to put technology at the service of desire. Although the conflict between desire and control was particularly thematized in Star Trek, most famously through the divided character of Spock, the practices of vidding are now applied to other visual texts. This essay examines the early history of vidding and demonstrates, through the close reading of particular vids made for Star Trek and Quantum Leap, how vidding heals the wounds created by the displacement and fragmentation of women on television.

  15. Late Cretaceous-Early Palaeogene tectonic development of SE Asia

    Science.gov (United States)

    Morley, C. K.

    2012-10-01

    The Late Cretaceous-Early Palaeogene history of the continental core of SE Asia (Sundaland) marks the time prior to collision of India with Asia when SE Asia, from the Tethys in the west to the Palaeo-Pacific in the east, lay in the upper plate of subduction zones. In Myanmar and Sumatra, subduction was interrupted in the Aptian-Albian by a phase of arc accretion (Woyla and Mawgyi arcs) and in Java, eastern Borneo and Western Sulawesi by collision of continental fragments rifted from northern Australia. Subsequent resumption of subduction in the Myanmar-Thailand sector explains: 1) early creation of oceanic crust in the Andaman Sea in a supra-subduction zone setting ~ 95 Ma, 2) the belt of granite plutons of Late Cretaceous-Early Palaeogene age (starting ~ 88 Ma) in western Thailand and central Myanmar, and 3) amphibolite grade metamorphism between 70 and 80 Ma seen in gneissic outcrops in western and central Thailand, and 4) accretionary prism development in the Western Belt of Myanmar, until glancing collision with the NE corner of Greater India promoted ophiolite obduction, deformation and exhumation of marine sediments in the early Palaeogene. The Ranong strike-slip fault and other less well documented faults, were episodically active during the Late Cretaceous-Palaeogene time. N to NW directed subduction of the Palaeo-Pacific ocean below Southern China, Vietnam and Borneo created a major magmatic arc, associated with rift basins, metamorphic core complexes and strike-slip deformation which continued into the Late Cretaceous. The origin and timing of termination of subduction has recently been explained by collision of a large Luconia continental fragment either during the Late Cretaceous or Palaeogene. Evidence for such a collision is absent from the South China Sea well and seismic reflection record and here collision is discounted. Instead relocation of the subducting margin further west, possibly in response of back-arc extension (which created the Proto

  16. In-vivo Centrifugation of Drosophila Embryos

    OpenAIRE

    Tran, Susan L.; Welte, Michael A.

    2010-01-01

    A major strategy for purifying and isolating different types of intracellular organelles is to separate them from each other based on differences in buoyant density. However, when cells are disrupted prior to centrifugation, proteins and organelles in this non-native environment often inappropriately stick to each other. Here we describe a method to separate organelles by density in intact, living Drosophila embryos. Early embryos before cellularization are harvested from population cages, an...

  17. UDP-galactose 4'-epimerase activities toward UDP-Gal and UDP-GalNAc play different roles in the development of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Jennifer M I Daenzer

    Full Text Available In both humans and Drosophila melanogaster, UDP-galactose 4'-epimerase (GALE catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal and UDP-glucose (UDP-glc in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc and UDP-N-acetylglucosamine (UDP-glcNAc. All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans.

  18. Asymmetric stem cell division: lessons from Drosophila.

    Science.gov (United States)

    Wu, Pao-Shu; Egger, Boris; Brand, Andrea H

    2008-06-01

    Asymmetric cell division is an important and conserved strategy in the generation of cellular diversity during animal development. Many of our insights into the underlying mechanisms of asymmetric cell division have been gained from Drosophila, including the establishment of polarity, orientation of mitotic spindles and segregation of cell fate determinants. Recent studies are also beginning to reveal the connection between the misregulation of asymmetric cell division and cancer. What we are learning from Drosophila as a model system has implication both for stem cell biology and also cancer research.

  19. Diversity. Early Developments. Volume 8, Number 1, Spring 2004

    Science.gov (United States)

    Manuel, John

    2004-01-01

    What is it about cultural diversity that challenges early childhood programs? One factor is that children enter early childhood and early intervention programs from families with a wide range of values and cultural experiences. Sometimes those values and experiences differ from those of the teachers and caregivers in those programs. Another factor…

  20. Ethnic Group Differences in Early Head Start Parents Parenting Beliefs and Practices and Links to Children's Early Cognitive Development

    Science.gov (United States)

    Keels, Micere

    2009-01-01

    Data from the Early Head Start Research and Evaluation study were used to examine the extent to which several factors mediate between- and within-ethnic-group differences in parenting beliefs and behaviors, and children's early cognitive development (analysis sample of 1198 families). The findings indicate that Hispanic-, European-, and…

  1. Improving Latino Children's Early Language and Literacy Development: Key Features of Early Childhood Education within Family Literacy Programmes

    Science.gov (United States)

    Jung, Youngok; Zuniga, Stephen; Howes, Carollee; Jeon, Hyun-Joo; Parrish, Deborah; Quick, Heather; Manship, Karen; Hauser, Alison

    2016-01-01

    Noting the lack of research on how early childhood education (ECE) programmes within family literacy programmes influence Latino children's early language and literacy development, this study examined key features of ECE programmes, specifically teacher-child interactions and child engagement in language and literacy activities and how these…

  2. Ethnic Group Differences in Early Head Start Parents Parenting Beliefs and Practices and Links to Children's Early Cognitive Development

    Science.gov (United States)

    Keels, Micere

    2009-01-01

    Data from the Early Head Start Research and Evaluation study were used to examine the extent to which several factors mediate between- and within-ethnic-group differences in parenting beliefs and behaviors, and children's early cognitive development (analysis sample of 1198 families). The findings indicate that Hispanic-, European-, and…

  3. Exploring Parental Involvement in Early Years Education in China: Development and Validation of the Chinese Early Parental Involvement Scale (CEPIS)

    Science.gov (United States)

    Lau, Eva Yi Hung; Li, Hui; Rao, Nirmala

    2012-01-01

    This study developed and validated an instrument, the Chinese Early Parental Involvement Scale (CEPIS), that can be widely used in both local and international contexts to assess Chinese parental involvement in early childhood education. The study was carried out in two stages: (1) focus group interviews were conducted with 41 teachers and 35…

  4. Improving Latino Children's Early Language and Literacy Development: Key Features of Early Childhood Education within Family Literacy Programmes

    Science.gov (United States)

    Jung, Youngok; Zuniga, Stephen; Howes, Carollee; Jeon, Hyun-Joo; Parrish, Deborah; Quick, Heather; Manship, Karen; Hauser, Alison

    2016-01-01

    Noting the lack of research on how early childhood education (ECE) programmes within family literacy programmes influence Latino children's early language and literacy development, this study examined key features of ECE programmes, specifically teacher-child interactions and child engagement in language and literacy activities and how these…

  5. Canonical Sonic Hedgehog Signaling in Early Lung Development

    Directory of Open Access Journals (Sweden)

    Hugo Fernandes-Silva

    2017-03-01

    Full Text Available The canonical hedgehog (HH signaling pathway is of major importance during embryonic development. HH is a key regulatory morphogen of numerous cellular processes, namely, cell growth and survival, differentiation, migration, and tissue polarity. Overall, it is able to trigger tissue-specific responses that, ultimately, contribute to the formation of a fully functional organism. Of all three HH proteins, Sonic Hedgehog (SHH plays an essential role during lung development. In fact, abnormal levels of this secreted protein lead to severe foregut defects and lung hypoplasia. Canonical SHH signal transduction relies on the presence of transmembrane receptors, such as Patched1 and Smoothened, accessory proteins, as Hedgehog-interacting protein 1, and intracellular effector proteins, like GLI transcription factors. Altogether, this complex signaling machinery contributes to conveying SHH response. Pulmonary morphogenesis is deeply dependent on SHH and on its molecular interactions with other signaling pathways. In this review, the role of SHH in early stages of lung development, specifically in lung specification, primary bud formation, and branching morphogenesis is thoroughly reviewed.

  6. Early influences and childhood development. Does helicobacter play a role?

    Science.gov (United States)

    Lee, Adrian

    2007-11-01

    In the late 1960s, Rene Dubos showed that a variety of nutritional stress in utero or in early infancy could have dramatic impact on childhood development that was irreversible. This included detectable changes in the brain. Since that time, iron deficiency anemia (IDA) has been identified as one of the major nutritional stresses that leads to permanent behavioral changes in both experimental animals and humans resulting in poorer cognitive, motor, and social-emotional function. It has been proposed that these changes play an important part in the inter-generational transmission of poverty. More recently, it is becoming clear that Helicobacter pylori causes IDA in populations on an iron-limiting diet. The main thesis of this article is that H. pylori infection may indeed have an impact on childhood development and that much more research is needed in this area as intervention via immunization or antimicrobial therapy in populations in the developing world may have major positive benefits via cure of IDA and prevention of brain damage in the young.

  7. Structural and Maturational Covariance in Early Childhood Brain Development.

    Science.gov (United States)

    Geng, Xiujuan; Li, Gang; Lu, Zhaohua; Gao, Wei; Wang, Li; Shen, Dinggang; Zhu, Hongtu; Gilmore, John H

    2017-03-01

    Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. The Early Stages of Heart Development: Insights from Chicken Embryos

    Directory of Open Access Journals (Sweden)

    Johannes G. Wittig

    2016-04-01

    Full Text Available The heart is the first functioning organ in the developing embryo and a detailed understanding of the molecular and cellular mechanisms involved in its formation provides insights into congenital malformations affecting its function and therefore the survival of the organism. Because many developmental mechanisms are highly conserved, it is possible to extrapolate from observations made in invertebrate and vertebrate model organisms to humans. This review will highlight the contributions made through studying heart development in avian embryos, particularly the chicken. The major advantage of chick embryos is their accessibility for surgical manipulation and functional interference approaches, both gain- and loss-of-function. In addition to experiments performed in ovo, the dissection of tissues for ex vivo culture, genomic, or biochemical approaches is straightforward. Furthermore, embryos can be cultured for time-lapse imaging, which enables tracking of fluorescently labeled cells and detailed analysis of tissue morphogenesis. Owing to these features, investigations in chick embryos have led to important discoveries, often complementing genetic studies in mice and zebrafish. As well as including some historical aspects, we cover here some of the crucial advances made in understanding early heart development using the chicken model.

  9. Initial neurogenesis in Drosophila

    OpenAIRE

    Hartenstein, Volker; Wodarz, Andreas

    2013-01-01

    Early neurogenesis comprises the phase of nervous system development during which neural progenitor cells are born. In early development, the embryonic ectoderm is subdivided by a conserved signaling mechanism into two main domains, the epidermal ectoderm and the neurectoderm. Subsequently, cells of the neurectoderm are internalized and form a cell layer of proliferating neural progenitors. In vertebrates, the entire neurectoderm folds into the embryo to give rise to the neural tube. In Droso...

  10. Impact of Early Postnatal Androgen Exposure on Voice Development

    Science.gov (United States)

    Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

    2012-01-01

    Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

  11. Impact of early postnatal androgen exposure on voice development.

    Directory of Open Access Journals (Sweden)

    Leila Grisa

    Full Text Available BACKGROUND: The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT in childhood. METHODS: The long-term effects of androgen exposure on the fundamental vocal frequency (F0, vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years and 10 adolescent (13.6 to 17.8 years female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. RESULTS: Of the 19 subjects, 17 (89% had been diagnosed with ACT before 4 years of age, 1 (5% at 8.16 years, and 1 (5% at 10.75 years. Androgen exposure (2 to 30 months was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19 of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. CONCLUSIONS: Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors.

  12. Origins and early development of human body knowledge.

    Science.gov (United States)

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

    As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensorimotor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuo-spatial body knowledge in infancy. Our technique is to compare infants'responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body picture sat 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial

  13. Drugs in early clinical development for the treatment of osteosarcoma.

    Science.gov (United States)

    Heymann, Marie-Françoise; Brown, Hannah K; Heymann, Dominique

    2016-11-01

    Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients. Areas covered: From the databases available and published scientific literature, the present review gives an overview of the drugs currently in early clinical development for the treatment of osteosarcoma. For each drug, a short description is given of the relevant scientific data supporting its development. Expert opinion: Multidrug targeted approaches are set to emerge, given the heterogeneity of osteosarcoma subtypes and the multitude of therapeutic responses. The key role played by the microenvironment in the disease increases the number of therapeutic targets (such as macrophages or osteoclasts), as well as the master proteins that control cell proliferation or cell death. Ongoing phase I/II trials are important steps, not only for identifying new therapies with greater safety and efficacy, but also for better defining the role played by the microenvironment in the pathogenesis of osteosarcoma.

  14. Early phonetic and lexical development: a productivity approach.

    Science.gov (United States)

    McCune, L; Vihman, M M

    2001-06-01

    Researchers frequently examine the development of the single-word lexicon in the absence of phonetic data. Yet a large body of literature demonstrates relationships between the phonetics of babble and early speech, and it is clear that production skill is essential for establishing a lexicon. This study uses longitudinal productivity criteria to establish children's phonetic skill. Twenty children were followed from age 9 to 16 months, and their level of consistency of vocal patterns was examined in relation to their lexical production, providing a relatively large-sample demonstration of phonetic/lexical relationships at the transition to language. Number of specific consonants produced consistently across the months of observation predicted referential lexical use at 16 months, whereas the transition to reference itself signaled the onset of a sharp increase in numbers of different words produced in a session. The earliest referential speakers exhibited prior consistency in the production of [p/b], which also predominated in their words. Prior use of at least two supraglottal consonants characterized the referential group. Children varied in the specific consonants they produced consistently, and these same consonants, varying according to individual child repertoire, characterized nearly all consonant-based words produced by each child in both of the final 2 months of observation. These findings are interpreted in relation to the children's contemporaneous development of representational ability and pragmatic skill.

  15. Discovery and early development of non-suppressed ion chromatography.

    Science.gov (United States)

    Fritz, James S; Gjerde, Douglas T

    2010-08-01

    This year marks the 30th anniversary of the publication of Non-Suppressed Ion Chromatography, which is a method for the rapid separation of anions with on-line conductimetric detection. In this method, the separation column is connected directly to the conductimetric detector. This single-column method is a simpler technique than the original suppressed ion chromatography method, which requires a large suppressor column to reduce the background conductance. In the new method, the background signal is reduced to a manageable level simply by using an ion-exchange separation column of low exchange capacity that lowers the eluent concentration needed for separation. The eluent ion used for separation is chosen based on having large, bulky structure, which lowers the equivalent conductance and facilitates detection of the sample anions. This is a personal account of the initial discovery and early development of non-suppressed ion chromatography. The circumstances for the discovery are recounted by the two authors. Methods are described for determination of anions, cations with indirect detection, and techniques for increasing detection sensitivity. A fundamental equation for the prediction of ion chromatography detector response is given, and the development of several types of detection schemes for ion chromatography is discussed. Finally, the impact of non-suppressed ion chromatography is discussed together with comments on the discovery process.

  16. Involvement of Notch signaling in early chick ovarian follicle development.

    Science.gov (United States)

    Li, Jun; Zhao, Dan; Guo, Changquan; Li, Jian; Mi, Yuling; Zhang, Caiqiao

    2016-01-01

    The formation of primordial follicles is a crucial process in the establishment of follicle pools required for the female's reproductive life span. For laying hens, ample follicles are a prerequisite for high laying performance. Notch signaling plays critical roles in germ cell cysts breakdown and in the formation of primordial follicles. Here, we investigated the role of Notch signaling in the ovarian development of post-hatch chicks. Results showed that around post-hatch day 4 (H4), the germ cell cysts broke apart, oocytes became surrounded by squamous pregranulosa cells, and the primordial follicles were then formed. Subsequently, we detected the expression of Notch signaling-related genes including Notch receptors (Notch1, 2), ligands (Jag1, 2 and Dll1, 4), and target genes (Hes1, Hey1). These genes all showed expression at H4 and some of these genes were up-regulated during primordial follicle formation. To evaluate the Notch signaling requirement for early follicular development, we adopted an in vitro ovary culture system. Suppression of Notch signaling by γ-secretase inhibitor induced a decrease of primordial follicles and an increase of germ cells in cysts. Attenuating Notch signaling also inhibited the phosphatidylinositol 3-kinase/protein kinase B pathways and suppressed cadherin expression. These results suggest that Notch signaling is endowed with an indispensable role in primordial follicle formation in post-hatch chicks.

  17. Drosophila Melanogaster as an Experimental Organism.

    Science.gov (United States)

    Rubin, Gerald M.

    1988-01-01

    Discusses the role of the fruit fly in genetics research requiring a multidisciplinary approach. Describes embryological and genetic methods used in the experimental analysis of this organism. Outlines the use of Drosophila in the study of the development and function of the nervous system. (RT)

  18. Drosophila Melanogaster as an Experimental Organism.

    Science.gov (United States)

    Rubin, Gerald M.

    1988-01-01

    Discusses the role of the fruit fly in genetics research requiring a multidisciplinary approach. Describes embryological and genetic methods used in the experimental analysis of this organism. Outlines the use of Drosophila in the study of the development and function of the nervous system. (RT)

  19. The embryo as a laboratory: quantifying transcription in Drosophila

    Science.gov (United States)

    Gregor, Thomas; Garcia, Hernan G.; Little, Shawn C.

    2014-01-01

    Transcriptional regulation of gene expression is fundamental to most cellular processes, including determination of cellular fates. Quantitative studies of transcription in cultured cells have led to significant advances in identifying mechanisms underlying transcriptional control. Recent progress allowed implementation of these same quantitative methods in multicellular organisms to ask how transcriptional regulation unfolds both in vivo and at the single molecule level in the context of embryonic development. Here we review some of these advances in early Drosophila development, which bring the embryo on par with its single-celled counterparts. In particular, we discuss progress in methods to measure mRNA and protein distributions in fixed and living embryos, and we highlight some initial applications that lead to fundamental new insights about molecular transcription processes. We end with an outlook on how to further exploit the unique advantages that come with investigating transcriptional control in the developmental context of the embryo. PMID:25005921

  20. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  1. ENU mutagenesis reveals that Notchless homolog 1 (Drosophila affects Cdkn1a and several members of the Wnt pathway during murine pre-implantation development

    Directory of Open Access Journals (Sweden)

    Lossie Amy C

    2012-12-01

    Full Text Available Abstract Background Our interests lie in determining the genes and genetic pathways that are important for establishing and maintaining maternal-fetal interactions during pregnancy. Mutation analysis targeted to a 34 Mb domain flanked by Trp53 and Wnt3 demonstrates that this region of mouse chromosome 11 contains a large number of essential genes. Two mutant alleles (l11Jus1 and l11Jus4, which fall into the same complementation group, survive through implantation but fail prior to gastrulation. Results Through a positional cloning strategy, we discovered that these homozygous mutant alleles contain non-conservative missense mutations in the Notchless homolog 1 (Drosophila (Nle1 gene. NLE1 is a member of the large WD40-repeat protein family, and is thought to signal via the canonical NOTCH pathway in vertebrates. However, the phenotype of the Nle1 mutant mice is much more severe than single Notch receptor mutations or even in animals in which NOTCH signaling is blocked. To test the hypothesis that NLE1 functions in multiple signaling pathways during pre-implantation development, we examined expression of multiple Notch downstream target genes, as well as select members of the Wnt pathway in wild-type and mutant embryos. We did not detect altered expression of any primary members of the Notch pathway or in Notch downstream target genes. However, our data reveal that Cdkn1a, a NOTCH target, was upregulated in Nle1 mutants, while several members of the Wnt pathway are downregulated. In addition, we found that Nle1 mutant embryos undergo caspase-mediated apoptosis as hatched blastocysts, but not as morulae or blastocysts. Conclusions Taken together, these results uncover potential novel functions for NLE1 in the WNT and CDKN1A pathways during embryonic development in mammals.

  2. Parvin overexpression uncovers tissue-specific genetic pathways and disrupts F-actin to induce apoptosis in the developing epithelia in Drosophila.

    Directory of Open Access Journals (Sweden)

    Maria Chountala

    Full Text Available Parvin is a putative F-actin binding protein important for integrin-mediated cell adhesion. Here we used overexpression of Drosophila Parvin to uncover its functions in different tissues in vivo. Parvin overexpression caused major defects reminiscent of metastatic cancer cells in developing epithelia, including apoptosis, alterations in cell shape, basal extrusion and invasion. These defects were closely correlated with abnormalities in the organization of F-actin at the basal epithelial surface and of integrin-matrix adhesion sites. In wing epithelium, overexpressed Parvin triggered increased Rho1 protein levels, predominantly at the basal side, whereas in the developing eye it caused a rough eye phenotype and severely disrupted F-actin filaments at the retina floor of pigment cells. We identified genes that suppressed these Parvin-induced dominant effects, depending on the cell type. Co-expression of both ILK and the apoptosis inhibitor DIAP1 blocked Parvin-induced lethality and apoptosis and partially ameliorated cell delamination in epithelia, but did not rescue the elevated Rho1 levels, the abnormal organization of F-actin in the wing and the assembly of integrin-matrix adhesion sites. The rough eye phenotype was suppressed by coexpression of either PTEN or Wech, or by knock-down of Xrp1. Two main conclusions can be drawn from our studies: (1, high levels of cytoplasmic Parvin are toxic in epithelial cells; (2 Parvin in a dose dependent manner affects the organization of actin cytoskeleton in both wing and eye epithelia, independently of its role as a structural component of the ILK-PINCH-Parvin complex that mediates the integrin-actin link. Thus, distinct genetic interactions of Parvin occur in different cell types and second site modifier screens are required to uncover such genetic circuits.

  3. Early, middle, and late Miocene basin development, California

    Energy Technology Data Exchange (ETDEWEB)

    Bachman, S.B.

    1988-03-01

    Contrary to earlier models of progressive basin development related to northward migration of the Mendocino triple junction, it can now be documented that the major basins of coastal California developed at about the same time in the late Oligocene to early Miocene. This basin development is marked by rapid deepening of basin floors, subsequent changes in depositional facies from nonmarine and shallow marine to deep marine, and widespread volcanism dated at 23-20 Ma. The coastal basins likely formed by rifting and subsidence linked to the proximity of the Farallon-pacific spreading ridge and the subduction of hot young oceanic crust, but cannot be correlated to any existing models of triple junction migration. Indeed, strike-slip restored positions of the coastal basins at their inception indicate that the basins were spread out over about 800 km of the southern coast of California. The Miocene basins were likely larger than the present coastal basins, although their configurations are obscured by late Neogene faulting and erosion. It is likely, however, that paleohighs separated at least some of the margin into proximal and distal basins. With local exceptions, structuring in the Miocene basins was primarily extensional, with widespread strike-slip and thrust tectonics restricted mainly to latest Miocene and younger events. Plate reconstructions suggest several hundred kilometers of transform motion occurred along the California margin during the Miocene, but there is only limited evidence of this movement in the known history of either the basins or the major faults of California. Sedimentation during the Miocene was controlled by both oceanic conditions (biogenic component) and the relative abundance of clastic input. The clastic input was controlled by a combination of proximal vs distal basinal positions, eustatic sea level changes, and local tectonics.

  4. Early childhood development interventions and cognitive development of young children in rural Vietnam.

    Science.gov (United States)

    Watanabe, Koichiro; Flores, Rafael; Fujiwara, Junko; Tran, Lien Thi Huong

    2005-08-01

    Little is known about the long-term benefits of interventions that aim to promote early childhood development programs. The goal of this research was to determine whether an early childhood development intervention added to a nutrition intervention during preschool ages had lasting effects on the cognitive development of school-age children in communes of Thanh Hoa province in rural Vietnam. The study focused on a total of 313 children aged 6.5-8.5 y (grades 1 and 2 in primary school) in 2 communes that were exposed to nutrition intervention or nutrition and early childhood development (ECD) intervention from 1999 to 2003. Measurements of height and cognitive test scores (Raven's Progressive Matrices Test) were collected from the children; household characteristics were determined by interviews with mothers. Longitudinal analysis was performed by integrating the data with that collected from the same children in past surveys. Significant effects of the ECD intervention compared with the nutrition intervention were detected. The beneficial effect of ECD intervention on the cognitive test scores was large for the most nutritionally challenged children whose height-for-age Z-scores declined or remained in the stunted range. The findings help provide useful insights into the development of an effective integrated model of ECD and nutrition intervention for children in rural Vietnam.

  5. [Early Intervention and Cognitive Development: A Longitudinal Study with Psychologically Stressed Mother-Child-Dyad during Early Childhood].

    Science.gov (United States)

    Zwönitzer, Annabel; Ziegenhain, Ute; Bovenschen, Ina; Pillhofer, Melanie; Spangler, Gottfried; Gerlach, Jennifer; Gabler, Sandra; Kindler, Heinz; Fegert, Jörg M; Künster, Anne Katrin

    2016-01-01

    Early intervention programs aiming at developing parents’ relationship and parenting skills and supporting young families have become increasingly established in Germany throughout the last decade. The present longitudinal study analyzed 53 children and their mothers receiving early intervention due to their psychosocially highly challenging life situations and personal circumstances. The children were examined at birth and at an age of twelve months as well as between ages two and four. The results revealed that the child’s cognitive development could be predicted by both maternal sensitivity and mother’s psychosocial stress. However, the amount, type, and intensity of early intervention did not have any effect on the child’s development. In terms of the effectiveness of early interventions the results implicate that interventions seems to be offered in an unspecific manner and does not contribute to an improvement of the child’s developmental status.

  6. Wealth Gradients in Early Childhood Cognitive Development in Five Latin American Countries

    OpenAIRE

    Schady, Norbert Rüdiger; Behrman, Jere R.; Araujo, María Caridad; Azuero, Rodrigo; Bernal, Raquel; Bravo, David; López Bóo, Florencia; Macours, Karen; Marshall, Daniela; Paxson, Christina H.; Vakis, Renos

    2014-01-01

    Research from the United States shows that gaps in early cognitive and noncognitive abilities appear early in the life cycle. Little is known about this important question for developing countries. This paper provides new evidence of sharp differences in cognitive development by socioeconomic status in early childhood for five Latin American countries. To help with comparability, the paper...

  7. The Development of Early Childhood Teachers' Language Knowledge in Different Educational Tracks

    Science.gov (United States)

    Strohmer, Janina; Mischo, Christoph

    2015-01-01

    Early childhood teachers should have extensive knowledge about language and language development, because these facets of professional knowledge are considered as important requirements for fostering language development in early childhood education settings. It is assumed that early childhood teachers acquire this knowledge during pre-service…

  8. Development of SED Camera for Quasars in Early Universe (SQUEAN)

    CERN Document Server

    Kim, Sanghyuk; Lee, Hye-In; Park, Woojin; Ji, Tae-Geun; Hyun, Minhee; Choi, Changsu; Im, Myungshin; Pak, Soojong

    2016-01-01

    We describe the characteristics and performance of a camera system, Spectral energy distribution Camera for Quasars in Early Universe (SQUEAN). It was developed to measure SEDs of high redshift quasar candidates (z $\\gtrsim$ 5) and other targets, e.g., young stellar objects, supernovae, and gamma-ray bursts, and to trace the time variability of SEDs of objects such as active galactic nuclei (AGNs). SQUEAN consists of an on-axis focal plane camera module, an auto-guiding system, and mechanical supporting structures. The science camera module is composed of a focal reducer, a customizable filter wheel, and a CCD camera on the focal plane. The filter wheel uses filter cartridges that can house filters with different shapes and sizes, enabling the filter wheel to hold twenty filters of 50 mm $\\times$ 50 mm size, ten filters of 86 mm $\\times$ 86 mm size, or many other combinations. The initial filter mask was applied to calibrate the filter wheel with high accuracy and we verified that the filter position is repea...

  9. Novel INHAT repressor (NIR) is required for early lymphocyte development.

    Science.gov (United States)

    Ma, Chi A; Pusso, Antonia; Wu, Liming; Zhao, Yongge; Hoffmann, Victoria; Notarangelo, Luigi D; Fowlkes, B J; Jain, Ashish

    2014-09-23

    Novel inhibitor of histone acetyltransferase repressor (NIR) is a transcriptional corepressor with inhibitor of histone acetyltransferase activity and is a potent suppressor of p53. Although NIR deficiency in mice leads to early embryonic lethality, lymphoid-restricted deletion resulted in the absence of double-positive CD4(+)CD8(+) thymocytes, whereas bone-marrow-derived B cells were arrested at the B220(+)CD19(-) pro-B-cell stage. V(D)J recombination was preserved in NIR-deficient DN3 double-negative thymocytes, suggesting that NIR does not affect p53 function in response to physiologic DNA breaks. Nevertheless, the combined deficiency of NIR and p53 provided rescue of DN3L double-negative thymocytes and their further differentiation to double- and single-positive thymocytes, whereas B cells in the marrow further developed to the B220(+)CD19(+) pro-B-cell stage. Our results show that NIR cooperate with p53 to impose checkpoint for the generation of mature B and T lymphocytes.

  10. Early experiences in developing and managing the neuroscience gateway

    Science.gov (United States)

    Sivagnanam, Subhashini; Majumdar, Amit; Yoshimoto, Kenneth; Astakhov, Vadim; Bandrowski, Anita; Martone, MaryAnn; Carnevale, Nicholas. T.

    2015-01-01

    SUMMARY The last few decades have seen the emergence of computational neuroscience as a mature field where researchers are interested in modeling complex and large neuronal systems and require access to high performance computing machines and associated cyber infrastructure to manage computational workflow and data. The neuronal simulation tools, used in this research field, are also implemented for parallel computers and suitable for high performance computing machines. But using these tools on complex high performance computing machines remains a challenge because of issues with acquiring computer time on these machines located at national supercomputer centers, dealing with complex user interface of these machines, dealing with data management and retrieval. The Neuroscience Gateway is being developed to alleviate and/or hide these barriers to entry for computational neuroscientists. It hides or eliminates, from the point of view of the users, all the administrative and technical barriers and makes parallel neuronal simulation tools easily available and accessible on complex high performance computing machines. It handles the running of jobs and data management and retrieval. This paper shares the early experiences in bringing up this gateway and describes the software architecture it is based on, how it is implemented, and how users can use this for computational neuroscience research using high performance computing at the back end. We also look at parallel scaling of some publicly available neuronal models and analyze the recent usage data of the neuroscience gateway. PMID:26523124

  11. Development of SED Camera for Quasars in Early Universe (SQUEAN)

    Science.gov (United States)

    Kim, Sanghyuk; Jeon, Yiseul; Lee, Hye-In; Park, Woojin; Ji, Tae-Geun; Hyun, Minhee; Choi, Changsu; Im, Myungshin; Pak, Soojong

    2016-11-01

    We describe the characteristics and performance of a camera system, Spectral energy distribution Camera for Quasars in Early Universe (SQUEAN). It was developed to measure SEDs of high-redshift quasar candidates (z ≳ 5) and other targets, e.g., young stellar objects, supernovae, and gamma-ray bursts, and to trace the time variability of SEDs of objects such as active galactic nuclei (AGNs). SQUEAN consists of an on-axis focal plane camera module, an autoguiding system, and mechanical supporting structures. The science camera module is composed of a focal reducer, a customizable filter wheel, and a CCD camera on the focal plane. The filter wheel uses filter cartridges that can house filters with different shapes and sizes, enabling the filter wheel to hold 20 filters of 50 mm × 50 mm size, 10 filters of 86 mm × 86 mm size, or many other combinations. The initial filter mask was applied to calibrate the filter wheel with high accuracy, and we verified that the filter position is repeatable at much less than one pixel accuracy. We installed and tested 50 nm medium bandwidth filters of 600–1050 nm and other filters at the commissioning observation in 2015 February. We found that SQUEAN can reach limiting magnitudes of 23.3–25.3 AB mag at 5σ in a one-hour total integration time.

  12. Early embryonic development and transplantation in tree shrews.

    Science.gov (United States)

    Yan, Lan-Zhen; Sun, Bin; Lyu, Long-Bao; Ma, Yu-Hua; Chen, Jia-Qi; Lin, Qing; Zheng, Ping; Zhao, Xu-Dong

    2016-07-18

    As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained (conception rate=74%). Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.

  13. Early environment and neurobehavioral development predict adult temperament clusters.

    Directory of Open Access Journals (Sweden)

    Eliza Congdon

    Full Text Available BACKGROUND: Investigation of the environmental influences on human behavioral phenotypes is important for our understanding of the causation of psychiatric disorders. However, there are complexities associated with the assessment of environmental influences on behavior. METHODS/PRINCIPAL FINDINGS: We conducted a series of analyses using a prospective, longitudinal study of a nationally representative birth cohort from Finland (the Northern Finland 1966 Birth Cohort. Participants included a total of 3,761 male and female cohort members who were living in Finland at the age of 16 years and who had complete temperament scores. Our initial analyses (Wessman et al., in press provide evidence in support of four stable and robust temperament clusters. Using these temperament clusters, as well as independent temperament dimensions for comparison, we conducted a data-driven analysis to assess the influence of a broad set of life course measures, assessed pre-natally, in infancy, and during adolescence, on adult temperament. RESULTS: Measures of early environment, neurobehavioral development, and adolescent behavior significantly predict adult temperament, classified by both cluster membership and temperament dimensions. Specifically, our results suggest that a relatively consistent set of life course measures are associated with adult temperament profiles, including maternal education, characteristics of the family's location and residence, adolescent academic performance, and adolescent smoking. CONCLUSIONS: Our finding that a consistent set of life course measures predict temperament clusters indicate that these clusters represent distinct developmental temperament trajectories and that information about a subset of life course measures has implications for adult health outcomes.

  14. Stage-specific proteome signatures in early bovine embryo development.

    Science.gov (United States)

    Deutsch, Daniela R; Fröhlich, Thomas; Otte, Kathrin A; Beck, Andrea; Habermann, Felix A; Wolf, Eckhard; Arnold, Georg J

    2014-10-03

    Development of early embryonic stages before activation of the embryonic genome depends on sufficiently stored products of the maternal genome, adequate recruitment and degradation of mRNAs, as well as activation, deactivation, and relocation of proteins. By application of an isobaric tagging for relative and absolute quantification (iTRAQ)-based approach, the proteomes of bovine embryos at the zygote and 2-cell and 4-cell stage with MII oocytes as a reference were quantitatively analyzed. Of 1072 quantified proteins, 87 differed significantly in abundance between the four stages. The proteomes of 2-cell and 4-cell embryos differed most from the reference MII oocyte, and a considerable fraction of proteins continuously increased in abundance during the stages analyzed, despite a strongly attenuated rate of translation reported for this period. Bioinformatic analysis revealed particularly interesting proteins involved in the p53 pathway, lipid metabolism, and mitosis. Verification of iTRAQ results by targeted SRM (selected reaction monitoring) analysis revealed excellent agreement for all five proteins analyzed. By principal component analysis, SRM quantifications comprising a panel of only five proteins were shown to discriminate between all four developmental stages analyzed here. For future experiments, an expanded SRM protein panel will provide the potential to detect developmental disturbances with high sensitivity and enable first insights into the underlying molecular pathways.

  15. Drosophila laminins act as key regulators of basement membrane assembly and morphogenesis.

    Science.gov (United States)

    Urbano, Jose M; Torgler, Catherine N; Molnar, Cristina; Tepass, Ulrich; López-Varea, Ana; Brown, Nicholas H; de Celis, Jose F; Martín-Bermudo, Maria D

    2009-12-01

    Laminins are heterotrimeric molecules found in all basement membranes. In mammals, they have been involved in diverse developmental processes, from gastrulation to tissue maintenance. The Drosophila genome encodes two laminin alpha chains, one beta and one Gamma, which form two distinct laminin trimers. So far, only mutations affecting one or other trimer have been analysed. In order to study embryonic development in the complete absence of laminins, we mutated the gene encoding the sole laminin beta chain in Drosophila, LanB1, so that no trimers can be made. We show that LanB1 mutant embryos develop until the end of embryogenesis. Electron microscopy analysis of mutant embryos reveals that the basement membranes are absent and the remaining extracellular material appears disorganised and diffuse. Accordingly, abnormal accumulation of major basement membrane components, such as Collagen IV and Perlecan, is observed in mutant tissues. In addition, we show that elimination of LanB1 prevents the normal morphogenesis of most organs and tissues, including the gut, trachea, muscles and nervous system. In spite of the above structural roles for laminins, our results unravel novel functions in cell adhesion, migration and rearrangement. We propose that while an early function of laminins in gastrulation is not conserved in Drosophila and mammals, their function in basement membrane assembly and organogenesis seems to be maintained throughout evolution.

  16. Chemical Cues Influence Pupation Behavior of Drosophila simulans and Drosophila buzzatii in Nature and in the Laboratory

    Science.gov (United States)

    Beltramí, Marcial; Medina-Muñoz, María Cristina; Del Pino, Francisco; Ferveur, Jean-Francois; Godoy-Herrera, Raúl

    2012-01-01

    In the wild, larvae of several species of Drosophila develop in heterogeneous and rapidly changing environments sharing resources as food and space. In this scenario, sensory systems contribute to detect, localize and recognize congeners and heterospecifics, and provide information about the availability of food and chemical features of environments where animals live. We investigated the behavior of D. simulans and D. buzzatii larvae to chemicals emitted by conspecific and heterospecific larvae. Our goal was to understand the role of these substances in the selection of pupation sites in the two species that cohabit within decaying prickly pear fruits (Opuntia ficus-indica). In these breeding sites, larvae of D. simulans and D. buzzatii detect larvae of the other species changing their pupation site preferences. Larvae of the two species pupated in the part of the fruit containing no or few heterospecifics, and spent a longer time in/on spots marked by conspecifics rather than heterospecifics. In contrast, larvae of the two species reared in isolation from conspecifics pupated randomly over the substrate and spent a similar amount of time on spots marked by conspecifics and by heterospecifics. Our results indicate that early chemically-based experience with conspecific larvae is critical for the selection of the pupation sites in D. simulans and D. buzzatii, and that pupation site preferences of Drosophila larvae depend on species-specific chemical cues. These preferences can be modulate by the presence of larvae of the same or another species. PMID:22737236

  17. Chemical cues influence pupation behavior of Drosophila simulans and Drosophila buzzatii in nature and in the laboratory.

    Directory of Open Access Journals (Sweden)

    Marcial Beltramí

    Full Text Available In the wild, larvae of several species of Drosophila develop in heterogeneous and rapidly changing environments sharing resources as food and space. In this scenario, sensory systems contribute to detect, localize and recognize congeners and heterospecifics, and provide information about the availability of food and chemical features of environments where animals live. We investigated the behavior of D. simulans and D. buzzatii larvae to chemicals emitted by conspecific and heterospecific larvae. Our goal was to understand the role of these substances in the selection of pupation sites in the two species that cohabit within decaying prickly pear fruits (Opuntia ficus-indica. In these breeding sites, larvae of D. simulans and D. buzzatii detect larvae of the other species changing their pupation site preferences. Larvae of the two species pupated in the part of the fruit containing no or few heterospecifics, and spent a longer time in/on spots marked by conspecifics rather than heterospecifics. In contrast, larvae of the two species reared in isolation from conspecifics pupated randomly over the substrate and spent a similar amount of time on spots marked by conspecifics and by heterospecifics. Our results indicate that early chemically-based experience with conspecific larvae is critical for the selection of the pupation sites in D. simulans and D. buzzatii, and that pupation site preferences of Drosophila larvae depend on species-specific chemical cues. These preferences can be modulate by the presence of larvae of the same or another species.

  18. Chemical cues influence pupation behavior of Drosophila simulans and Drosophila buzzatii in nature and in the laboratory.

    Science.gov (United States)

    Beltramí, Marcial; Medina-Muñoz, María Cristina; Del Pino, Francisco; Ferveur, Jean-Francois; Godoy-Herrera, Raúl

    2012-01-01

    In the wild, larvae of several species of Drosophila develop in heterogeneous and rapidly changing environments sharing resources as food and space. In this scenario, sensory systems contribute to detect, localize and recognize congeners and heterospecifics, and provide information about the availability of food and chemical features of environments where animals live. We investigated the behavior of D. simulans and D. buzzatii larvae to chemicals emitted by conspecific and heterospecific larvae. Our goal was to understand the role of these substances in the selection of pupation sites in the two species that cohabit within decaying prickly pear fruits (Opuntia ficus-indica). In these breeding sites, larvae of D. simulans and D. buzzatii detect larvae of the other species changing their pupation site preferences. Larvae of the two species pupated in the part of the fruit containing no or few heterospecifics, and spent a longer time in/on spots marked by conspecifics rather than heterospecifics. In contrast, larvae of the two species reared in isolation from conspecifics pupated randomly over the substrate and spent a similar amount of time on spots marked by conspecifics and by heterospecifics. Our results indicate that early chemically-based experience with conspecific larvae is critical for the selection of the pupation sites in D. simulans and D. buzzatii, and that pupation site preferences of Drosophila larvae depend on species-specific chemical cues. These preferences can be modulate by the presence of larvae of the same or another species.

  19. Early Holocene lake ecosystem development in the southern Baltic lowlands

    Science.gov (United States)

    Słowiński, Michał; Ott, Florian; Kramkowski, Mateusz; Noryśkiewicz, Agnieszka M.; Zawiska, Izabela; Dräger, Nadine; Theuerkauf, Martin; Hass, Christoph; Obremska, Milena; Błaszkiewicz, Mirosław; Kordowski, Jarosław; Tjallingii, Rik; Rzodkiewicz, Monika; Schwab, Markus; Brauer, Achim

    2016-04-01

    The first millennia of the Holocene are characterized by gradual and rapid environmental changes following the warming at the beginning of the Holocene superimposed by short-term climatic instability. Landscape evolution during this period occurred at different time scales due to specific response times of landscape compartments like vegetation succession, soil formation and permafrost thawing. As a consequence, a spatiotemporally heterogeneous pattern of changes occurred particularly in regions close to the margins of the continental ice sheets like the Baltic region. Regional atmospheric circulation patterns were affected by cold catabatic winds from the remains of the Fennoscandian ice sheet. The ongoing deglaciation further influenced the regional climate through meltwater release and related changes in the North Atlantic thermohaline circulation. Both effects declined with the progressive ice sheet melt down. Additionally, the land-sea distribution in the North Sea changed drastically during the final melting phase of the glacial ice sheets. The Baltic Sea development is even more complex due to the strong glacio-isostatic adjustments effects that resulted in open and closed water stages affecting the entire Baltic realm. Consequently, the early Holocene interval of sediment records from the southern Baltic lowlands are not considered as straightforward palaeoclimate archives but need to be interpreted in a broader context. We present five partly varved lake records from northern Poland all including an intriguing highly organic-rich interval interrupting biochemical calcite precipitation at about the same time between 10.5 and 10.2 cal kyr BP. These sediment records have been correlated by independent age models based on varve counting, AMS 14C dating, biostratigraphy and tephrochronology. We present multi-proxy records of early Holocene sediments and our preliminary interpretation suggests hydrological processes as the main reason for the intriguing shifts

  20. Microfluidic system with integrated microinjector for automated Drosophila embryo injection.

    Science.gov (United States)

    Delubac, Daniel; Highley, Christopher B; Witzberger-Krajcovic, Melissa; Ayoob, Joseph C; Furbee, Emily C; Minden, Jonathan S; Zappe, Stefan

    2012-11-21

    Drosophila is one of the most important model organisms in biology. Knowledge derived from the recently sequenced 12 genomes of various Drosophila species can today be combined with the results of more than 100 years of research to systematically investigate Drosophila biology at the molecular level. In order to enable automated, high-throughput manipulation of Drosophila embryos, we have developed a microfluidic system based on a Pyrex-silicon-Pyrex sandwich structure with integrated, surface-micromachined silicon nitride injector for automated injection of reagents. Our system automatically retrieves embryos from an external reservoir, separates potentially clustered embryos through a sheath flow mechanisms, passively aligns an embryo with the integrated injector through geometric constraints, and pushes the embryo onto the injector through flow drag forces. Automated detection of an embryo at injection position through an external camera triggers injection of reagents and subsequent ejection of the embryo to an external reservoir. Our technology can support automated screens based on Drosophila embryos as well as creation of transgenic Drosophila lines. Apart from Drosophila embryos, the layout of our system can be easily modified to accommodate injection of oocytes, embryos, larvae, or adults of other species and fills an important technological gap with regard to automated manipulation of multicellular organisms.