Sox8 and Sox9 influence differentiation and nuclear positioning of retinal Muller glia [CUT&RUN]

Sox8 and Sox9, members of the SoxE transcription factor family, are highly expressed in late-stage retinal progenitor cells and mature Müller glia (MG), yet their functional roles remain incompletely defined. Here we employed gain- and loss-of-function approaches, single-cell multiomic profiling, and injury models to investigate Sox8/9 function.

Overexpression of Sox8 and/or Sox9 in early-stage RPCs suppressed early-born cell fates and promoted photoreceptor generation, consistent with a role in late-stage temporal identity. Conversely, conditional deletion of Sox8 and/or Sox9 in late-stage progenitors did not impair MG specification, but caused radial displacement of MG nuclei into the outer retina and modest changes in glial gene expression. Loss of Sox8/9 in mature MG modestly increased proliferation post-injury without inducing neurogenic competence.