title: A transient wave of BMP signaling in the retina is necessary for Müller glial differentiation.
abstract: The primary glial cells in the retina, the Müller glia, differentiate from retinal progenitors in the first postnatal week. CNTF/LIF/STAT3 signaling has been shown to promote their differentiation; however, another key glial differentiation signal, BMP, has not been examined during this period of Müller glial differentiation. In the course of our analysis of the BMP signaling pathway, we observed a transient wave of Smad1/5/8 signaling in the inner nuclear layer at the end of the first postnatal week, from postnatal day (P) 5 to P9, after the end of neurogenesis. To determine the function of this transient wave, we blocked BMP signaling during this period in vitro or in vivo, using either a BMP receptor antagonist or noggin (Nog). Either treatment leads to a reduction in expression of the Müller glia-specific genes Rlbp1 and Glul, and the failure of many of the Müller glia to repress the bipolar/photoreceptor gene Otx2. These changes in normal Müller glial differentiation result in permanent disruption of the retina, including defects in the outer limiting membrane, rosette formation and a reduction in functional acuity. Our results thus show that Müller glia require a transient BMP signal at the end of neurogenesis to fully repress the neural gene expression program and to promote glial gene expression.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ueki
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Wilken
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Cox
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Chipman
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Bermingham-McDonogh
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, USA tomreh@uw.edu.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Reh
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D063928:Ependymoglial Cells / Q000502:physiology*; D055879:Gene Knock-In Techniques; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000254:growth & development*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; C499317:Ascl1 protein, mouse
keywords: Glia; Id1; Mouse; Neurogenesis; Smad