Atoh7-independent specification of retinal ganglion cell identity

Abstract

Retinal ganglion cells (RGCs), which relay visual information from the eye to the brain, are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor Atoh7, which is expressed in multipotent early neurogenic retinal progenitor cells, leads to a selective and near complete loss of RGCs. Atoh7 has thus been considered essential for conferring competence on progenitors to generate RGCs. However, when apoptosis is inhibited in Atoh7-deficient mice by loss of function of Bax, only a modest reduction in RGC number is observed. Single-cell RNA-Seq of Atoh7;Bax-deficient retinas shows that RGC differentiation is delayed, but that RGC precursors are 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-independent mechanisms for RGC specification.