GENE NETWORKS IN DROSOPHILA MELANOGASTER EYE DEVELOPMENT

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 对调节分化的机制的理解显然与对癌症和许多其他疾病的理解和治疗相关，并且对于使体外组织分化或从干细胞分化成为现实是必要的。组织类型的分化由差异基因表达引起，部分在转录组水平上调节。同源结构域转录因子Pax 6在果蝇、小鼠和人类等多种后生动物中调节眼睛特异性基因表达。由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非常复杂，传统的遗传学方法无法解开单个因素之间的关系。我们需要的是对所涉及的基因以及它们如何相互作用的完整知识。大规模并行测序的最新进展使转录组分析的新方法成为可能。要完全理解调节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Pax 6）的内在输入如何与来自信号通路的外在输入整合。利用D.作为模型，大规模平行测序将用于鉴定可能由Pax 6和对眼睛发育重要的信号传导途径共调节的转录靶点。随后，将使用计算方法来鉴定具有相似表达谱的基因，并鉴定由Pax 6直接调控的基因和这些信号通路的核效应子。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.