Atoh7-independent specification of retinal ganglion cell identity

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 factorAtoh7, which is expressed in multipotent early neurogenic retinal progenitor cells, leads to a selective and near complete loss of RGCs.Atoh7has thus been considered essential for conferring competence on progenitors to generate RGCs. However, when apoptosis is inhibited inAtoh7-deficient mice by loss of function ofBax, only a modest reduction in RGC number is observed. Single-cell RNA-Seq ofAtoh7;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 forAtoh7in RGC survival, and demonstratesAtoh7-independent mechanisms for RGC specification.