title: Cas adaptor proteins organize the retinal ganglion cell layer downstream of integrin signaling.
abstract: Stratification of retinal neuronal cell bodies and lamination of their processes provide a scaffold upon which neural circuits can be built. However, the molecular mechanisms that direct retinal ganglion cells (RGCs) to resolve into a single-cell retinal ganglion cell layer (GCL) are not well understood. The extracellular matrix protein laminin conveys spatial information that instructs the migration, process outgrowth, and reorganization of GCL cells. Here, we show that the β1-Integrin laminin receptor is required for RGC positioning and reorganization into a single-cell GCL layer. β1-Integrin signaling within migrating GCL cells requires Cas signaling-adaptor proteins, and in the absence of β1-Integrin or Cas function retinal neurons form ectopic cell clusters beyond the inner-limiting membrane (ILM), phenocopying laminin mutants. These data reveal an essential role for Cas adaptor proteins in β1-Integrin-mediated signaling events critical for the formation of the single-cell GCL in the mammalian retina.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Riccomagno
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Lu O
authors.initials: LO
authors.lastname: Sun
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Brady
authors.affiliation: Department of Medicine, Division of Clinical Immunology, The Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Alexandropoulos
authors.affiliation: Department of Hematology & Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Seo
authors.affiliation: Department of Hematology & Oncology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: kolodkin@jhmi.edu.
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D000818:Animals; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D019012:Integrin beta1; D007797:Laminin