Atoh7-independent specification of retinal ganglion cell identity

Justin Brodie-Kommit, Brian S. Clark, Qing Shi, Fion Shiau, Dong Won Kim, Jennifer Langel, Catherine Sheely, Philip A. Ruzycki, Michel Fries, Awais Javed, Michel Cayouette, Tiffany Schmidt, Tudor Badea, Tom Glaser, Haiqing Zhao, Joshua Singer, Seth Blackshaw, Samer Hattar

Research output: Contribution to journalArticlepeer-review

Abstract

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor Atoh7, expressed in multipotent early neurogenic retinal progenitors leads to a selective and essentially complete loss of RGCs. Therefore, Atoh7 is considered essential for conferring competence on progenitors to generate RGCs. Despite the importance of Atoh7 in RGC specification, we find that inhibiting apoptosis in Atoh7-deficient mice by loss of function of Bax only modestly reduces RGC numbers. Single-cell RNA sequencing of Atoh7;Bax-deficient retinas shows that RGC differentiation is delayed but that the gene expression profile of RGC precursors is grossly normal. Atoh7;Baxdeficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry but exhibit severe axonal guidance defects. This study reveals an essential role for Atoh7 in RGC survival and demonstrates Atoh7dependent and Atoh7-independent mechanisms for RGC specification.

Original languageEnglish (US)
Article numbereabe4983
JournalScience Advances
Volume7
Issue number11
DOIs
StatePublished - Mar 12 2021

ASJC Scopus subject areas

  • General

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