title: Sox2-Deficient Müller Glia Disrupt the Structural and Functional Maturation of the Mammalian Retina.
abstract: OBJECTIVE
  Müller glia (MG), the principal glial cells of the vertebrate retina, display quiescent progenitor cell characteristics. They express key progenitor markers, including the high mobility group box transcription factor SOX2 and maintain a progenitor-like morphology. In the embryonic and mature central nervous system, SOX2 maintains neural stem cell identity. However, its function in committed Müller glia has yet to be determined.
  
  
  METHODS
  We use inducible, MG-specific genetic ablation of Sox2 in vivo at the peak of MG genesis to analyze its function in the maturation of murine MG and effects on other cells in the retina. Histologic and functional analysis of the Sox2-deficient retinas is conducted at key points in postnatal development.
  
  
  RESULTS
  Ablation of Sox2 in the postnatal retina results in disorganization of MG processes in the inner plexiform layer and mislocalized cell bodies in the nuclear layers. This disorganization is concurrent with a thinning of the neural retina and disruption of neuronal processes in the inner and outer plexiform layers. Functional analysis by electroretinography reveals a decrease in the b-wave amplitude. Disruption of MG maturation due to Sox2 ablation therefore negatively affected the function of the retina.
  
  
  CONCLUSIONS
  These results demonstrate a novel role for SOX2 in glial process outgrowth and adhesion, and provide new insights into the essential role Müller glia play in the development of retinal cytoarchitecture. Prior to this work, SOX2 was known to have a primary role in determining cell fate. Our experiments bypass cell fate conversion to establish a new role for SOX2 in a committed cell lineage.
authors.affiliation: Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States 2Curriculum in Neurobiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States.
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Bachleda
authors.affiliation: Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States 3Department of Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States.
authors.forename: Larysa H
authors.initials: LH
authors.lastname: Pevny
authors.affiliation: Neuroscience Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States 4Department of Cell Biology and Physiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, United States 5Lineberger Comprehe.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Weiss
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004596:Electroretinography; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D012313:RNA / Q000235:genetics*; D012160:Retina / Q000502:physiology* / Q000648:ultrastructure; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D055748:SOXB1 Transcription Factors; D012313:RNA