GENE NETWORKS IN DROSOPHILA MELANOGASTER EYE DEVELOPMENT

果蝇眼睛发育中的基因网络

• 批准号: 8167584
• 负责人: JENNIFER R CURTISS
• 金额: $ 10.85万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167584
• 关键词: Complex; Computer Retrieval of Information on Scientific Projects Database; Disease; Drosophila genus; Drosophila melanogaster; Eye; Eye Development; Funding; Gene Expression; Gene Expression Profile; Genes; Genetic; Grant; Histocompatibility Testing; Human; In Vitro; Individual; Institution; Knowledge; Modeling; Molecular Profiling; Mus; Nuclear; Research; Research Personnel; Resources; Signal Pathway; Source; Stem cells; Tissue Differentiation; Tissue-Specific Gene Expression; Tissues; United States National Institutes of Health; cancer therapy; homeodomain; novel strategies; transcription factor

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 了解调节分化的机制显然与理解和治疗癌症和许多其他疾病相关，并且对于实现体外组织分化或干细胞分化是必要的。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。