OTX2 represses sister cell fate choices in the developing retina to promote photoreceptor specification

During vertebrate retinal development, subsets of progenitor cells generate progeny in a non-stochastic manner, suggesting that these decisions are tightly regulated. However, the gene-regulatory network components that are functionally important in these progenitor cells are largely unknown.

OTX2 is required for the generation of photoreceptors, but also for repression of specific retinal fates and alternative gene regulatory networks. These include specific subtypes of retinal ganglion and horizontal cells, suggesting that in this context, OTX2 functions to repress sister cell fate choices.

Taken together, the current study proposes a model in which OTX2 serves as a key positive regulator of photoreceptor genesis from restricted RPCs, while repressing specific subtypes of other retinal fates (Figure 7M). At the gene regulatory network level, OTX2 represses key transcription factors involved in non-photoreceptor cell types (Figure 7N). Further combined use of the single cell sequencing/CRISPR gene editing approach with variation of time, targeted genes, and labeled cell populations will provide a powerful genetic strategy to examine developmental gene regulatory networks.