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

Cell Rep. 2019 Apr 16;27(3):900-915.e5. doi: 10.1016/j.celrep.2019.03.077.

Abstract

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.

Keywords: J-RGC; Jam2; OFF RGC; OFF-sustained RGC; RGC development; RGC subtype; Tbr1; dendritic branching; dendritic morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Axons / pathology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cholera Toxin / toxicity
  • Dendrites / physiology
  • Embryo, Mammalian / metabolism
  • Mice
  • Mice, Transgenic
  • Patch-Clamp Techniques
  • Potassium / pharmacology
  • Retina / growth & development
  • Retina / metabolism
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / pathology
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*

Substances

  • Cell Adhesion Molecules
  • Jam2 protein, mouse
  • T-Box Domain Proteins
  • Tbr1 protein, mouse
  • Cholera Toxin
  • Potassium