Biomaterial Database

Atoh7-independent specification of retinal ganglion cell identity. 2021

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

Department of Biology, Johns Hopkins University, Baltimore, MD, USA.

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;Bax-deficient 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 Atoh7-dependent and Atoh7-independent mechanisms for RGC specification.