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

项目总结

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.