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

项目摘要 光是昼夜节律生物学、行为和基因表达的重要调节器。光- 触发的视觉功能通过多个渠道协调，并由特定的 视网膜神经节细胞（RGC）类型。尽管我们在理解 40+ RGC类型的形态和功能， 不同RGC类型的形成和存活仍然知之甚少。这份拨款申请 关注T-box转录因子Tbr 1和Tbr 2在调节特定类型的 视网膜神经节细胞（RGCs）。我们以前发现Tbr 1表达标志着两种不同的 Tbr 1在调节树突状细胞形态发生中起着关键作用 在这些RGC中。我们已经表明，Tbr 2是形成和维持 ipRGC的存活。最近，我们进一步发现表达Tbr 2的神经元是 由两个种群组成。这个项目的目标是了解基因调控 通过Tbr 1和Tbr 2介导的网络，以全面了解 这些不同的RGC在发育过程中形成。我们将通过以下方式实现这一目标： Tbr 1及其转录网络在发育调控中的作用和功能， 树突状形态发生。我们将分析视网膜离体投射， ipRGC亚型，研究Tbr 2下游调节因子Irx 1在ipRGC发生中的作用。 ipRGC亚型，阐明Tbr 2+置换的无长突细胞的身份和Tbr 2在 这些dAC，并在发育过程中建立Tbr 2介导的RGC到RGC/dAC网络。 本申请的目的是了解研资局亚型的设计原则 视网膜回路的结构和功能。完成拟议项目 将建立更深入的了解如何两个密切相关的转录因子的功能 在调节不同RGC亚型的发展方面如此不同。

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.