13 research outputs found

    Drosophila blastoderm patterning

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    The Drosophila blastoderm embryo is a classic model for the study of the genetics of pattern formation. In recent years, quantitative empirical approaches have been employed extensively in the study of blastoderm pattern formation. This quantitative work has enabled the development of a number of data-driven computational models. More than in other systems, these models have been experimentally validated, and have informed new empirical work. They have led to insights into the establishment of morphogen gradients, the interpretation and transduction of positional information by downstream transcriptional networks, and the mechanisms by which spatial scaling and robustness of gene expression are achieved. Here we review the latest developments in the field

    Temporal and spatial dynamics of scaling-specific features of a gene regulatory network in Drosophila

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    A widely appreciated aspect of developmental robustness is pattern formation in proportion to size. But how such scaling features emerge dynamically remains poorly understood. Here we generate a data set of the expression profiles of six gap genes in Drosophila melanogasterembryos that differ significantly in size. Expression patterns exhibit size-dependent dynamics both spatially and temporally. We uncover a dynamic emergence of under-scaling in the posterior, accompanied by reduced expression levels of gap genes near the middle of large embryos. Simulation results show that a size-dependent Bicoid gradient input can lead to reduced Krüppel expression that can have long-range and dynamic effects on gap gene expression in the posterior. Thus, for emergence of scaled patterns, the entire embryo may be viewed as a single unified dynamic system where maternally derived size-dependent information interpreted locally can be propagated in space and time as governed by the dynamics of a gene regulatory network

    Multimodal transcriptional control of pattern formation in embryonic development

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    Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes

    Multimodal transcriptional control of pattern formation in embryonic development

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    Predicting how interactions between transcription factors and regulatory DNA sequence dictate rates of transcription and, ultimately, drive developmental outcomes remains an open challenge in physical biology. Using stripe 2 of the even-skipped gene in Drosophila embryos as a case study, we dissect the regulatory forces underpinning a key step along the developmental decision-making cascade: the generation of cytoplasmic mRNA patterns via the control of transcription in individual cells. Using live imaging and computational approaches, we found that the transcriptional burst frequency is modulated across the stripe to control the mRNA production rate. However, we discovered that bursting alone cannot quantitatively recapitulate the formation of the stripe and that control of the window of time over which each nucleus transcribes even-skipped plays a critical role in stripe formation. Theoretical modeling revealed that these regulatory strategies (bursting and the time window) respond in different ways to input transcription factor concentrations, suggesting that the stripe is shaped by the interplay of 2 distinct underlying molecular processes

    Binary transcriptional control of pattern formation in development

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    During development, stochastic promoter switching between active and inactive states results in transcriptional bursts. We tested whether burst kinetics are sufficient to quantitatively recapitulate the formation of patterns of accumulated mRNA in Drosophila embryos by dissecting the transcriptional dynamics of even-skipped stripe 2. Using a novel memory-adjusted hidden Markov model, single-cell live imaging and theoretical modeling, we show that the regulation of bursting in space and time alone is insufficient to predict stripe formation. In addition to bursting, we discovered that the duration of the window of time over which genes transcribe is regulated, and that this binary (on/off) control of where and when gene expression occurs, not transcriptional bursting, is the main regulatory strategy governing stripe formation. Thus, a quantitative description of the regulation of both bursting and the transcriptional time window are necessary to capture the full complement of molecular rules governing the transcriptional control of pattern formation

    Molecular determinants of Min protein pattern formation

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    Molecular determinants of Min protein pattern formation

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    Molecular determinants of Min protein pattern formation

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