GENE NETWORKS IN DROSOPHILA MELANOGASTER EYE DEVELOPMENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 对分化调控机制的理解显然与癌症和许多其他疾病的理解和治疗有关，而且对于使组织在体外或从干细胞分化成为现实是必要的。组织类型的分化是基因表达差异的结果，基因表达的差异部分是在转录组水平上调节的。同源结构域转录因子Pax6调节各种后生动物的眼睛特异基因表达，如果蝇、黑腹果蝇、老鼠和人类。信号通路提供的时间和空间信息对眼睛发育也是必不可少的。然而，控制眼睛发育的转录网络极其复杂，仅靠传统的遗传方法无法理清个体因素之间的关系。我们需要的是对所涉及的基因以及它们如何相互作用的全面了解。大规模平行测序的最新进展使转录组分析的新方法成为可能。要完全理解调控眼睛分化的转录网络，需要了解来自组织特异性转录因子(如Pax6)的内部输入如何与来自信号通路的外部输入整合。以黑腹毛虫的眼睛为模型，大规模平行测序将被用来识别可能由Pax6和对眼睛发育重要的信号通路共同调节的转录靶标。随后，将使用计算方法来识别具有相似表达谱的基因，并识别由Pax6和这些信号通路的核效应因子直接调控的基因。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An understanding of the mechanisms regulating differentiation is clearly relevant to understanding and treatment of cancer and many other diseases, and will be necessary to make tissue differentiation in vitro or from stem cells a reality. Differentiation of tissue types results from differential gene expression, regulated in part at the level of the transcriptome. The homeodomain transcription factor Pax6 regulates eye-specific gene expression in such diverse metazoans as the fruit fly Drosophila melanogaster, mice and humans. Temporal and spatial information provided by signaling pathways is also essential for eye development. However, the transcriptional networks that govern eye development are extremely complex, and traditional genetic approaches alone have not been able to untangle the relationships among the individual factors. What is needed is a complete knowledge of the genes involved and how they interact with one another. Recent advances in massively parallel sequencing have made possible new approaches to transcriptome analysis. A complete understanding of the transcriptional networks that regulate differentiation of the eye will require knowledge of how the intrinsic input from tissue-specific transcription factors like Pax6 is integrated with extrinsic input from signaling pathways. Using the D. melanogaster eye as a model, massively parallel sequencing will be used to identify transcriptional targets potentially co-regulated by Pax6 and by signaling pathways important for eye development. Subsequently, computational approaches will be used to identify genes with similar expression profiles, and to identify genes directly regulated by Pax6 and the nuclear effectors of these signaling pathways.