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）：发育中的组织依赖于多种生化途径的整合来调节神经分化。 EGF 受体和 Notch 信号传导对于这一过程至关重要，调节这些途径之间的平衡对于限制分化为神经元的细胞数量至关重要。在发育中的脊椎动物眼睛中，形成的第一种细胞类型是视网膜神经节细胞（RGC）； RGC 对于将视觉信息传递和传递到大脑至关重要。 RGC 的分化需要转录因子 Ath5 的表达，并且形成的 RGC 数量受到 Notch 信号转导途径活性的限制。同样，在发育中的果蝇眼睛中，第一种细胞类型（R8 光感受器）的分化需要 Ath5 同源物 Atonal 的表达；该表达也受到Notch活性的限制。该提案旨在阐明两种 Ig 超家族细胞粘附分子在果蝇眼睛发育过程中调节 Notch 和 EGF 受体信号传导的活性。 Echinoid (ed) 和 Friend of Echinoid (fred) 是同源跨膜蛋白；这些基因的突变会破坏 R8 光受体的无调性表达和正常模式。 Spencer 博士建议通过各种遗传、分子和生化方法来研究 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，并鉴定与它们直接相关的蛋白质。这些实验将进一步加深我们对细胞粘附分子在调节信号通路中的作用以及驱动视网膜分化的线索的理解。脊椎动物中调节 RGC 分化的途径与果蝇中 R8 的调节途径之间的相似性表明，这项工作也将及时拓宽我们对调节 RGC 形成的基因的理解。