( ) is a critical early regulator of retinal pigment epithelial development.

Unlabelled: Myelin regulatory factor (Myrf) is a critical transcription factor in early retinal and retinal pigment epithelial development, and human variants in are a cause for nanophthalmos. Single cell RNA sequencing (scRNAseq) was performed on conditional knockout mice ( ) at 3 developmental timepoints. was expressed specifically in the RPE, and expression was abrogated in eyes. scRNAseq analysis revealed a loss of RPE cells at all timepoints resulting from cell death. GO-term analysis in the RPE revealed downregulation of melanogenesis and anatomic structure morphogenesis pathways, which were supported by electron microscopy and histologic analysis. Novel structural target genes including and , along with macular degeneration and inherited retinal disease genes were identified as downregulated, and a strong upregulation of TGFß/BMP signaling and effectors was observed. Regulon analysis placed downstream of and and upstream of in RPE differentiation. Together, these results suggest a strong role for Myrf in the RPE maturation by regulating melanogenesis, cell survival, and cell structure, in part acting through suppression of TGFß signaling and activation of .

Summary Statement: regulates RPE development, melanogenesis, and is important for cell structure and survival, in part through regulation of , and and BMP/TGFb signaling.