Information about features in the visual world is parsed by circuits in the retina and is then transmitted to the brain by distinct subtypes of retinal ganglion cells (RGCs). Axons from RGC subtypes are stratified in retinorecipient brain nuclei, such as the superior colliculus (SC), to provide a segregated relay of parallel and feature-specific visual streams. Here, we sought to identify the molecular mechanisms that direct the stereotyped laminar targeting of these axons. We focused on ipsilateral-projecting subtypes of RGCs (ipsiRGCs) whose axons target a deep SC sublamina. We identified an extracellular glycoprotein, Nephronectin (NPNT), whose expression is restricted to this ipsiRGC-targeted sublamina. SC-derived NPNT and integrin receptors expressed by ipsiRGCs are both required for the targeting of ipsiRGC axons to the deep sublamina of SC. Thus, a cell-extracellular matrix (ECM) recognition mechanism specifies precise laminar targeting of ipsiRGC axons and the assembly of eye-specific parallel visual pathways.

Center for Neurobiology Research Fralin Biomedical Research Institute at Virginia Tech Carilion Roanoke VA 24016

Center for Neurobiology Research Fralin Biomedical Research Institute at Virginia Tech Carilion Roanoke VA 24016;

Center for Neuroscience Research Children's National Medical Center Washington DC 20010

Department of Biological Sciences Virginia Tech Blacksburg VA 24061

Department of Biomedical Sciences and Pathobiology Virginia Maryland College of Veterinary Medicine Virginia Tech Blacksburg VA 24061

Department of Experimental Neurobiology National Institute of Mental Health Klecany 250 67 Czech Republic

Department of Pediatrics The George Washington University School of Medicine and Health Sciences Washington DC 20052

Department of Pediatrics Virginia Tech Carilion School of Medicine Roanoke VA 24016

Department of Pharmacology and Physiology The George Washington University School of Medicine and Health Sciences Washington DC 20052

Department of Psychiatry and Behavioral Medicine Virginia Tech Carilion School of Medicine Roanoke VA 24016

Graduate Program in Translational Biology Medicine and Health Virginia Tech Blacksburg VA 24061

School of Neuroscience Virginia Tech Blacksburg VA 24061

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