Sox15 is a novel retinal developmental gene that promotes cone photoreceptor differentiation through inhibition of alternative rod photoreceptor fates

The type of cell fate decisions a progenitor can make in the developing nervous system are dependent on a combination of cell intrinsic gene expression programs and cell extrinsic signaling molecules that influence expression programs. Moreover, both the progenitor’s spatial location in the tissue and time at which it exists during development can, to varying degrees, influence the competency of differentiation. Here, we use the developing mouse retina to understand how signaling factors in the retinal niche can influence a progenitor to become unipotentially restricted to differentiate into cone photoreceptors, and how this competency changes over the course of retinal development. We show that the secreted inhibitory protein COCO causes progenitors to become cone restricted, and that the competency for this restricted differentiation is maintained throughout retinal development. Using RNA-sequencing, we identify the transcription factor Sox15 as a potential novel marker of restricted progenitors in the developing retina, and that it acts in response to COCO’s effects. Knockdown experiments indicate that this novel retinal transcription factor is involved in the survival of retinal progenitors and promotes cone differentiation by inhibiting differentiation into alternative photoreceptor types.