The transcription factor Tbx5 regulates direction-selective retinal ganglion cell development and image stabilization

Timour Al-Khindi, Michael B. Sherman, Takashi Kodama, Preethi Gopal, Zhiwei Pan, James K. Kiraly, Hao Zhang, Loyal A. Goff, Sascha du Lac, Alex L. Kolodkin

Research output: Contribution to journalArticlepeer-review

Abstract

The diversity of visual input processed by the mammalian visual system requires the generation of many distinct retinal ganglion cell (RGC) types, each tuned to a particular feature. The molecular code needed to generate this cell-type diversity is poorly understood. Here, we focus on the molecules needed to specify one type of retinal cell: the upward-preferring ON direction-selective ganglion cell (up-oDSGC) of the mouse visual system. Single-cell transcriptomic profiling of up- and down-oDSGCs shows that the transcription factor Tbx5 is selectively expressed in up-oDSGCs. The loss of Tbx5 in up-oDSGCs results in a selective defect in the formation of up-oDSGCs and a corresponding inability to detect vertical motion. A downstream effector of Tbx5, Sfrp1, is also critical for vertical motion detection but not up-oDSGC formation. These results advance our understanding of the molecular mechanisms that specify a rare retinal cell type and show how disrupting this specification leads to a corresponding defect in neural circuitry and behavior.

Original languageEnglish (US)
Pages (from-to)4286-4298.e5
JournalCurrent Biology
Volume32
Issue number19
DOIs
StatePublished - Oct 10 2022

Keywords

  • direction-selectivity
  • eye movements
  • neural development
  • retina
  • retinal ganglion cell
  • single-cell RNA-seq

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology

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