title: SOX2 maintains the quiescent progenitor cell state of postnatal retinal Muller glia.
abstract: Within discrete regions of the developing mammalian central nervous system, small subsets of glia become specialized to function as neural stem cells. As a result of their self-renewal and neurogenic capacity, these cells later serve to replenish neurons and glia during persistent or injury-induced adult neurogenesis. SOX2, an HMG box transcription factor, plays an essential role in the maintenance of both embryonic and adult neural progenitors. It is unclear, however, which biological mechanisms regulated by SOX2 are required for neural stem cell maintenance. In this study, we address this question through genetic analysis of SOX2 function in differentiating postnatal Müller glia, a cell type that maintains neurogenic capacity in the adult retina. By utilizing molecular analysis and real-time imaging, we show that two progenitor characteristics of nascent Müller glia - their radial morphology and cell cycle quiescence - are disrupted following conditional genetic ablation of Sox2 in the mouse postnatal retina, leading to Müller cell depletion and retinal degeneration. Moreover, we demonstrate that genetic induction of the Notch signaling pathway restores Müller glial cell identity to Sox2 mutant cells, but does not secure their quiescent state. Collectively, these results uncouple the roles of SOX2 and the Notch signaling pathway in the postnatal retina, and uncover a novel role for SOX2 in preventing the depletion of postnatal Müller glia through terminal cell division.
authors: UNC Neuroscience Center, Department of Genetics, University of North Carolina, 115 Mason Farm Road, Chapel Hill, NC 27599, USA. nsurzenko@genetics.med.harvard.edu
authors: Natalia
authors: N
authors: Surzenko
authors: Tessa
authors: T
authors: Crowl
authors: Amelia
authors: A
authors: Bachleda
authors: Lee
authors: L
authors: Langer
authors: Larysa
authors: L
authors: Pevny
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse