Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse

Abstract

Summary: In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Here, we demonstrate that T-box transcription factor T-brain 1 (Tbr1) is expressed in two groups of morphologically and functionally distinct RGCs: the orientation-selective J-RGCs and a group of OFF-sustained RGCs with symmetrical dendritic arbors. When Tbr1 is genetically ablated during retinal development, these two RGC groups cannot develop. Ectopically expressing Tbr1 in M4 ipRGCs during development alters dendritic branching and density but not the inner plexiform layer stratification level. Our data indicate that Tbr1 plays critical roles in regulating the formation and dendritic morphogenesis of specific RGC types. : Little is known about how diversified retinal ganglion cell (RGC) subtypes develop. Using genetic and electrophysiological analyses, Kiyama et al. identify Tbr1 expression in two types of morphologically and functionally distinct OFF RGCs. Loss-of-function and gain-of-function studies show Tbr1 regulates the formation and dendritic morphogenesis of these cells. Keywords: Tbr1, RGC development, RGC subtype, J-RGC, Jam2, OFF-sustained RGC, OFF RGC, dendritic branching, dendritic morphogenesis