Atoh7-independent specification of retinal ganglion cell identity
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 factorAtoh7, expressed in multipotent early neurogenic retinal progenitors leads to a selective and essentially complete loss of RGCs. Therefore,Atoh7is considered essential for conferring competence on progenitors to generate RGCs. Despite the importance of Atoh7 in RGC specification, we find that inhibiting apoptosis inAtoh7-deficient mice by loss of function ofBaxonly modestly reduces RGC numbers. Single-cell RNA sequencing ofAtoh7;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 forAtoh7in RGC survival and demonstratesAtoh7-dependent andAtoh7-independent mechanisms for RGC specification.