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

June 2021 in “ Developmental biology ”

Venkata Thulabandu, Timothy Nehila, J. Ferguson, Radhika P. Atit

EZH2 Polycomb Repressive Complex 2 PRC2 methyltransferase Wnt/β-catenin signaling retinoic acid RA signaling fibroblast differentiation epidermal proliferation keratinocyte development secondary hair follicle initiation Wnt signaling RA hair follicle initiation

TLDR Dermal EZH2 controls skin cell development and hair growth in mice.

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.

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