Dermal EZH2 Orchestrates Dermal Differentiation and Epidermal Proliferation During Murine Skin Development

This study identifies dermal EZH2, a methyltransferase enzyme of the Polycomb Repressive Complex 2 (PRC2), as a key regulator in murine skin development. Dermal EZH2 is crucial for dermal fibroblast differentiation and spatial restriction of Wnt/β-catenin signaling, reinforcing fibroblast cell fate. It also regulates reticular dermal markers and secondary hair follicle initiation. Embryos lacking dermal Ezh2 exhibit increased epidermal proliferation and differentiation, which can be mitigated by inhibiting retinoic acid (RA) signaling. Thus, dermal EZH2 modulates Wnt/β-catenin and RA signaling to influence fibroblast differentiation and epidermal keratinocyte development.