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Laminar organization within the vertebrate retinal inner plexiform layer (IPL) facilitates pre- and postsynaptic neurite targeting, yet the precise mechanisms underlying establishment of functional IPL subdomains are not well understood. Here, we explore mechanisms defining the compartmentalization of OFF and ON neurites generally, and OFF and ON direction-selective neurites specifically, within the developing mouse IPL. We show that semaphorin 6A (Sema6A), a repulsive axon guidance cue, is required for delineation of OFF versus ON circuits within the IPL: in the Sema6a null IPL, the boundary between OFF and ON domains is blurred. Furthermore, Sema6A expressed by retinal ganglion cells (RGCs) directs laminar segregation of OFF and ON starburst amacrine cell dendritic scaffolds, which themselves serve as a substrate upon which other retinal neurites elaborate. These results demonstrate that RGCs, the first type of neuron born within the retina, play an active role in functional specialization of the IPL.<\/jats:p>","DOI":"10.1242\/dev.204293","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T15:08:03Z","timestamp":1730732883000},"source":"Crossref","is-referenced-by-count":11,"title":["Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the mouse inner retina"],"prefix":"10.1242","volume":"151","author":[{"given":"Rebecca E.","family":"James","sequence":"first","affiliation":[{"name":"Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins School of Medicine 1 The Solomon H. Snyder Department of Neuroscience , , 725 North Wolfe Street, Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie R.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins School of Medicine 1 The Solomon H. Snyder Department of Neuroscience , , 725 North Wolfe Street, Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola Nicole","family":"Huffman","sequence":"additional","affiliation":[{"name":"Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins School of Medicine 1 The Solomon H. Snyder Department of Neuroscience , , 725 North Wolfe Street, Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Brown","sequence":"additional","affiliation":[{"name":"Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins School of Medicine 1 The Solomon H. Snyder Department of Neuroscience , , 725 North Wolfe Street, Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria N.","family":"Neckles","sequence":"additional","affiliation":[{"name":"Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins School of Medicine 1 The Solomon H. Snyder Department of Neuroscience , , 725 North Wolfe Street, Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Jeroen","family":"Pasterkamp","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht Brain Center, Utrecht University 2 Department of Translational Neuroscience , , Universiteitsweg 100, 3584 CG, Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loyal A.","family":"Goff","sequence":"additional","affiliation":[{"name":"Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins School of Medicine 1 The Solomon H. Snyder Department of Neuroscience , , 725 North Wolfe Street, Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-5513","authenticated-orcid":false,"given":"Alex L.","family":"Kolodkin","sequence":"additional","affiliation":[{"name":"Johns Hopkins Kavli Neuroscience Discovery Institute, The Johns Hopkins School of Medicine 1 The Solomon H. Snyder Department of Neuroscience , , 725 North Wolfe Street, Baltimore, MD 21205 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"2024112613460772500_DEV204293C67","doi-asserted-by":"publisher","first-page":"pdb.prot5273","DOI":"10.1101\/pdb.prot5273","article-title":"Dissection, plating, and maintenance of cortical astrocyte cultures","volume":"8","author":"Albuquerque","year":"2009","journal-title":"Cold Spring Harbor Protoc."},{"key":"2024112613460772500_DEV204293C68","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1007\/s00018-016-2137-x","article-title":"Transmembrane semaphorins, forward and reverse signaling: have a look both ways","volume":"73","author":"Battistini","year":"2016","journal-title":"Cell. Mol. 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