Meeting Abstract
Continuous neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. Whether similar mechanisms regulate the transition from proliferation toward differentiation during both early and late stages of eye development is currently unknown. In this study, we analyse two small eye mutants that exhibit reduced CMZs and carry lesions in gdf6a, a BMP family member previously implicated in dorsal eye specification. We show that gdf6a mutant eyes exhibit expanded Retinoic Acid (RA) activity and go on to demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors similar to gdf6a mutants. We provide evidence that RA encourages cell cycle exit and regulates the timing of RPC differentiation during both early and late neurogenesis, showing that over-activation of the RA pathway accelerates retinal neurogenesis whereas its inhibition in gdf6a mutants re-establishes appropriate timing of retinal neurogenesis and restores retinal stem and progenitor cell populations in the CMZ. Together, our results support a model by which dorsally expressed Gdf6a balances RA pathway activity during early and late neurogenesis to control the transition from proliferation toward differentiation in the growing eye.
