Roles of Fred and Ed in Retinal Neurogenesis (AREA)

Fred 和 Ed 在视网膜神经发生 (AREA) 中的作用

• 批准号: 7128045
• 负责人: SUSAN A SPENCER
• 金额: $ 22.05万
• 依托单位: SAINT LOUIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7128045
• 关键词: Drosophilidae; cell adhesion molecules; extracellular; intracellular; neurogenesis; proteins; receptor; role; training; university

DESCRIPTION (provided by applicant): Developing tissues rely on the integration of several biochemical pathways to regulate neural differentiation. Both EGF-Receptor and Notch signaling are essential to this process, and modulating the balance between these pathways is critical in limiting the number of cells that differentiate as neurons. In the developing vertebrate eye, the first cell type to form is the retinal ganglion cell (RGC); RGCs are essential for transducing and relaying visual information to the brain. Differentiation of RGCs requires expression of the transcription factor Ath5, and the number of RGCs that form is limited by activity of the Notch signal transduction pathway. Similarly, in the developing Drosophila eye, differentiation of the first cell type, the R8 photoreceptor, requires expression of the Ath5 homolog Atonal; this expression is also limited by Notch activity. This proposal seeks to elucidate the activities of two Ig-superfamily cell adhesion molecules that modulate Notch and EGF-Receptor signaling during Drosophila eye development. Echinoid (ed) and Friend of Echinoid (fred) are homologous transmembrane proteins; mutations in these genes disrupt expression of Atonal and normal patterning of R8 photo receptors. Through a variety of genetic, molecular, and biochemical approaches, Dr. Spencer proposes to examine the roles of Ed and Fred in retinal development, characterize the functions of their intracellular and extracellular domains, and identify the proteins with which they associate directly. These experiments will further our understanding of the roles of cell adhesion molecules in modulating signaling pathways, and of the cues that drive retinal differentiation. The similarity between the pathways that regulate differentiation of RGCs in vertebrates and R8s in Drosophila suggests that this work will in time also broaden our understanding of the genes that regulate RGC formation.

描述（由申请人提供）：开发组织依赖于几种生化途径的整合来调节神经分化。 EGF受体和Notch信号对于此过程都是必不可少的，并且调节这些途径之间的平衡对于限制区分为神经元的细胞数量至关重要。在发育中的脊椎动物眼中，第一种形成的细胞类型是视网膜神经节细胞（RGC）。 RGC对于将视觉信息传递到大脑至关重要。 RGC的分化需要表达转录因子ATH5，并且形成的RGC数量受到Notch信号转导途径的活性的限制。同样，在发育中的果蝇眼中，第一种细胞类型的分化R8光感受器需要表达Ath5同源物atonal。该表达也受到Notch活性的限制。该提案旨在阐明两个在果蝇眼发发育过程中调节缺口和EGF受体信号传导的两个Ig-蛋白酶细胞粘附分子的活性。棘突（ED）和棘突（Fred）的朋友是同源的跨膜蛋白。这些基因中的突变破坏了R8照片受体的原始和正常图案的表达。通过多种遗传，分子和生化方法，Spencer博士建议检查ED和FRED在视网膜发育中的作用，表征其细胞内和细胞外结构域的功能，并直接鉴定与它们直接关联的蛋白质。这些实验将进一步理解细胞粘附分子在调节信号通路和驱动视网膜分化的提示中的作用。调节果蝇中脊椎动物和R8S中RGC分化的途径之间的相似性表明，这项工作将及时扩大我们对调节RGC形成的基因的理解。