Atoh7-independent specification of retinal ganglion cell identity

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 <i>Atoh7</i>, expressed in multipotent early neurogenic retinal progenitors leads to a selective and essentially complete loss of RGCs. Therefore, <i>Atoh7</i> 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 <i>Atoh7-</i>deficient mice by loss of function of <i>Bax</i> only modestly reduces RGC numbers. Single-cell RNA sequencing of <i>Atoh7;Bax</i>-deficient retinas shows that RGC differentiation is delayed but that the gene expression profile of RGC precursors is grossly normal. <i>Atoh7;Bax</i>-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 <i>Atoh7</i> in RGC survival and demonstrates <i>Atoh7</i>-dependent and <i>Atoh7-</i>independent mechanisms for RGC specification.