Smarcc1 drives optic stalk patterning and optic nerve head astrocyte differentiation

Here, we define the progression of astrocyte formation from the optic stalk and identify stage‑specific functions of the SWI/SNF scaffolding subunits Smarcc1 (Baf155) and Smarcc2 (Baf170). 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 (ONH) morphogenesis, resulting in glial lamina collapse, RGC 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/Sox2 activity.