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Here, we define the progression of astrocyte formation from the optic stalk and identify stage-specific functions of the SWI\/SNF scaffolding subunits Smarcc1 and Smarcc2. Both factors are co-expressed in retinal pigment epithelium (RPE) and optic stalk progenitors, with Smarcc2 persisting in differentiated RPE and astrocytes. Conditional deletion using Dct-Cre revealed compensatory activity in pigmented lineages, whereas Smarcc1 loss uniquely disrupted optic nerve head morphogenesis, resulting in glial lamina collapse, retinal ganglion cell degeneration and progressive visual decline. Spatial transcriptomics and functional assays show that Smarcc1 enables dorsal optic stalk progenitors to transition from a pigmented, RPE-like state to astrocyte progenitors by repressing pigment gene programs and permitting Pax2 and Sox2 activity. After specification, Smarcc1 is also required for glial lamina assembly and astrocyte migration into the inner retina. These findings demonstrate that Smarcc1-dependent chromatin remodeling coordinates astrocyte specification with optic nerve head morphogenesis to maintain long-term retinal function.<\/jats:p>","DOI":"10.1242\/dev.205769","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:34:55Z","timestamp":1786617295000},"source":"Crossref","is-referenced-by-count":0,"title":["Smarcc1 drives optic stalk patterning and optic nerve head astrocyte differentiation"],"prefix":"10.1242","volume":"153","author":[{"given":"Nitay","family":"Zuk-Bar","sequence":"first","affiliation":[{"name":"Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Gray Faculty of Medical & Health Sciences and Sagol School of Neurosciences , , Tel Aviv 69978 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai","family":"Ovadia","sequence":"additional","affiliation":[{"name":"Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Gray Faculty of Medical & Health Sciences and Sagol School of Neurosciences , , Tel Aviv 69978 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-2773","authenticated-orcid":false,"given":"Guizhong","family":"Cui","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory, School of Basic Medical Sciences, Guangzhou Medical University 2 , Guangzhou 510005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Obolensky","sequence":"additional","affiliation":[{"name":"Center for Retinal and Macular Degenerations, Department of Ophthalmology, Hadassah Medical Center and Hebrew University Faculty of Medicine 3 Faculty of Medicine , , Jerusalem 91120 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Banin","sequence":"additional","affiliation":[{"name":"Center for Retinal and Macular Degenerations, Department of Ophthalmology, Hadassah Medical Center and Hebrew University Faculty of Medicine 3 Faculty of Medicine , , Jerusalem 91120 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-3113","authenticated-orcid":false,"given":"Ron","family":"Ofri","sequence":"additional","affiliation":[{"name":"Food and Environment, Hebrew University of Jerusalem 4 Faculty of Agriculture , , Rehovot 7610001 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naihe","family":"Jing","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory, School of Basic Medical Sciences, Guangzhou Medical University 2 , Guangzhou 510005 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