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

The study demonstrated that dermal EZH2, an enzyme in the Polycomb Repressive Complex 2, played a crucial role in coordinating dermal differentiation and epidermal proliferation during murine skin development. Dermal EZH2 was essential for dermal fibroblast differentiation by spatially restricting Wnt/β-catenin signaling and later regulated the differentiation into reticular dermal fibroblasts and the initiation of secondary hair follicles. Embryos lacking dermal Ezh2 exhibited increased epidermal proliferation and differentiation, which could be mitigated by inhibiting retinoic acid signaling. Thus, dermal EZH2 acted as a regulator of Wnt/β-catenin and RA signaling, affecting both fibroblast differentiation and epidermal keratinocyte development.