SOX2 is critical for the maintenance of quiescence and homeostasis in nascent Muller glial cells

SOX2 is a HMG-box transcription factor that defines neural stem cell populations from the earliest stages of embryogenesis to adulthood. Previous studies have shown that SOX2 is critical for specifying neural competence in retinal progenitor cells in early mouse optic cup development, but its function in postnatal retinal progenitor cells is largely unexplored. Moreover, SOX2 expression is maintained in the adult retina in a population of Muller glia, which retain progenitor characteristics and have the capacity to generate neurons following injury, although our understanding of the role of SOX2 in Muller glia of the developing retina is limited. In this study, via conditional and specific ablation, we address the functions of SOX2 in both postnatal retinal progenitors and in Muller glia in the developing retina. Our hypothesis is that SOX2 is essential for cell cycle dynamics, progenitor cell identity, and homeostasis in both postnatal retinal progenitor cells and in differentiated Muller glia. We find that loss of SOX2 in postnatal progenitors results in the degradation of Muller glia morphology and the entrance of Muller glia into the cell cycle. Additionally, we find that hypomorphic levels of SOX2 during early retinal development induced Muller glia proliferation in late development. Lastly, we report that Muller glia proliferation is enhanced during their gliotic stress response.;In neural stem/progenitor cells, there are networks of basic helix-loop-helix (bHLH) transcription factors that regulate proliferation and differentiation. In this study, we address whether the misexpression of proneural bHLH factors, specifically Neurogenin-2 (NGN2), affects cell fate choices in postnatal retinal progenitors. Our hypothesis is that bHLH factor misexpression will influence retinal progenitors to undergo neurogenesis at the expense of gliogenesis. We find that NGN2-misexpressing cells preferentially become amacrine neurons and rod photoreceptors and avoid the Muller glial cell fate. This result indicates that NGN2 is capable of influencing retinal progenitors to generate neurons at the expense of glial cells and encourages the production of amacrine cells over other retinal neurons.