Roles of T-box transcriptional regulators in the development of RGC subtypes

项目摘要 光是昼夜节律、行为和基因表达的重要调节因子。光- 触发的视觉功能通过多个渠道编排，并由特定的 视网膜神经节细胞(RGC)类型。尽管我们对这一问题的理解取得了重大进展 40+RGC类型的形态和功能，支持RGC的细胞和分子基础 不同类型的研资局的形成和存活仍然知之甚少。这项拨款建议 重点阐述了T-box转录因子Tbr1和Tbr2在调节特定类型的 视网膜神经节细胞(RGC)。我们之前已经发现，Tbr1的表达标志着两个不同的 Off RGC的亚群，并且Tbr1在调节树突状细胞的形态发生中起关键作用 在这些RGC中。我们已经证明了Tbr2对于形成和维持 IpRGC的存活。最近，我们进一步发现，表达Tbr2的神经元 由两个种群组成。本项目的目标是了解基因调控 由Tbr1和Tbr2介导的网络，以全面了解 这些不同的RGC是在发育过程中形成的。我们将通过下定决心实现这一目标 Tbr1及其转录网络在调节发育和发育中的作用和功能 视网膜节细胞发育中树突状细胞的形态发生。我们将分析视网膜脱离的投射 IpRGC亚型，研究Tbr2下游调控因子Irx1在肿瘤发生发展中的作用 IpRGC亚型，阐明Tbr2+移位的无长突细胞的特性以及Tbr2在 这些DAC，并在发育过程中建立Tbr2介导的RGC到RGC/DAC网络。 此应用程序的目标是了解RGC子类型背后的设计原则 视网膜环路的形成和结构与功能。拟建项目竣工 将加深对两个密切相关的转录因子如何发挥作用的理解 因此，在调控不同RGC亚型的发育方面存在差异。

Project Summary Light is an important regulator in circadian biology, behavior, and gene expression. Light- triggered visual functions are orchestrated through multiple channels and conveyed by specific retinal ganglion cell (RGC) types. Despite significant progress in our understanding of the morphologies and functions of the 40+ RGC types, the cellular and molecular basis underlying the formation and survival of the diverse RGC types remains poorly understood. This grant proposal focuses on the roles of T-box transcription factors Tbr1 and Tbr2 in regulating specific types of retinal ganglion cells (RGCs). We have previously found that Tbr1 expression marks two distinct subsets of OFF RGCs, and that Tbr1 plays a critical role in regulating the dendritic morphogenesis in these RGCs. We have shown that Tbr2 is essential for the formation and maintaining the survival of ipRGCs. Most recently, we further discovered that Tbr2-expressing neurons are comprised of two populations. The goals of this project are to understand the genetic regulatory networks mediated by Tbr1 and Tbr2 in order to gain a comprehensive understanding of how these distinct RGCs are formed during development. We will accomplish this goal by determining the role and function of Tbr1 and its transcriptional network in regulating development and dendritic morphogenesis in developing RGCs. We will analyze the retinofugal projections of ipRGC subtype, investigate the role of Tbr2 downstream regulator Irx1 in the development of ipRGC subtype, elucidate the identity of Tbr2+ displaced amacrine cells and the role of Tbr2 in these dACs, and establish Tbr2-mediated RGC-to-RGC/dAC networks during development. The objective of this application is to understand the design principle underlying RGC subtype formation and the structure and function of retinal circuits. Completion of the proposed project will build deeper understanding regarding how two closely related transcription factors function so differently in regulating the development of distinct RGC subtypes.