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Class 5 transmembrane semaphorins control selective Mammalian retinal lamination and function |
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| Authors: | Matsuoka Ryota L Chivatakarn Onanong Badea Tudor C Samuels Ivy S Cahill Hugh Katayama Kei-Ichi Kumar Sumit R Suto Fumikazu Chédotal Alain Peachey Neal S Nathans Jeremy Yoshida Yutaka Giger Roman J Kolodkin Alex L |
| Institution: | 1 The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 2 Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 3 Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA 4 Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA 5 Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA 6 Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA 7 Division of Developmental Biology, Cincinnati Children''s Hospital Medical Center, Cincinnati, OH 45229, USA 8 Retinal Circuit Development & Genetics Unit, Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, MD 20892, USA 9 Departments of Ultrastructural Research, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan 10 Institut National de la Santé et de la Recherche Médicale (INSERM), UMR S968, Institut de la Vision, F-75012 Paris, France 11 Université Pierre et Marie Curie (UPMC) Paris VI, UMR S968, Institut de la Vision, F-75012 Paris, France 12 Centre National de la Recherche Scientifique (CNRS) UMR 7210, Institut de la Vision, F-75012 Paris, France 13 Research Service, Cleveland VA Medical Center, Cleveland, OH 44106, USA |
| Abstract: | In the vertebrate retina, neurites from distinct neuronal cell types are constrained within the plexiform layers, allowing for establishment of retinal lamination. However, the mechanisms by which retinal neurites are segregated within the inner or outer plexiform layers are not known. We find that the transmembrane semaphorins Sema5A and Sema5B constrain neurites from multiple retinal neuron subtypes within the inner plexiform layer (IPL). In Sema5A?/?; Sema5B?/? mice, retinal ganglion cells (RGCs) and amacrine and bipolar cells exhibit severe defects leading to neurite mistargeting into the outer portions of the retina. These targeting abnormalities are more prominent in the outer (OFF) layers of the IPL and result in functional defects in select RGC response properties. Sema5A and Sema5B inhibit retinal neurite outgrowth through PlexinA1 and PlexinA3 receptors both in vitro and in vivo. These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function. |
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