POU4F2/BRN3B overexpression promotes the genesis of retinal ganglion cell-like projection neurons from late progenitors.

Abstract

Retinal ganglion cells (RGCs) are the projection neurons of the retina, and their death promotes an irreversible blindness. Several factors were described to control their genesis during retinal development which include Atoh7 as a major orchestrator for RGC program and downstream targets, including Pou4f factors, which in turn regulate key aspects of terminal differentiation. The absence of POU4F family genes results in defects in RGC differentiation, aberrant axonal elaboration and ultimately RGC death, confirming the requirement of POU4F factors for RGC development and survival, with a critical role in regulating RGC axon outgrowth and pathfinding. Here, we investigated in vivo whether ectopic Pou4f2 expression in late retinal progenitor cells (late RPCs) is sufficient to induce the generation of cells with RGC properties, including long range axon projections. We showed that Pou4f2 overexpression generates RGC-like cells that share morphological and transcriptional features with RGCs normally generated during early development and extend axonal projections up to the brain. In conclusion, these results showed that POU4F2 alone was sufficient to promote critical properties of projection neurons from retinal progenitors outside their developmental window.