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Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development

Katherine L Dauber1, Carolina N Perdigoto1, Victor J Valdes1

  • 1Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

The Journal of Investigative Dermatology
|March 21, 2016
PubMed

Insights

Polycomb repressive complex 2 (PRC2) is crucial for skin development. Ablating PRC2 subunits (EED, Suz12, Ezh1/2) in skin progenitors revealed distinct lineage-specific roles, impacting epidermal barrier, Merkel cells, and hair follicles.

Area of Science:

  • Developmental Biology
  • Epigenetics
  • Stem Cell Biology

Background:

  • Polycomb repressive complex 2 (PRC2) regulates cell physiology and stem cell control.
  • Previous studies focused on single PRC2 subunit loss, overlooking potential independent functions.
  • Emerging evidence suggests PRC2 subunits may operate outside the complex.

Purpose of the Study:

  • To investigate the role of PRC2 in embryonic skin development.
  • To determine if PRC2 subunits function as a complex or independently in skin progenitors.
  • To analyze the lineage-specific effects of PRC2 ablation in the epidermis, hair follicles, and Merkel cells.

Main Methods:

  • Generation and analysis of three conditional knockout mouse lines targeting EED, Suz12, and Ezh1/2 in embryonic epidermal progenitors.
  • Conditional ablation of essential PRC2 subunits in vivo.
  • Phenotypic analysis of skin development, epidermal barrier formation, Merkel cell differentiation, and hair follicle morphogenesis.

Main Results:

  • Loss-of-function phenotypes were consistent across EED, Suz12, and Ezh1/2 knockouts, confirming their role as PRC2 complex subunits in skin epithelium.
  • PRC2 absence led to premature epidermal barrier acquisition.
  • Ectopic Merkel cell formation and defective hair follicle development were observed in PRC2-deficient skin.

Conclusions:

  • EED, Suz12, and Ezh1/2 function primarily as integral components of PRC2 within the skin epithelium.
  • PRC2 plays distinct and critical roles in the development of different skin lineages.
  • The absence of PRC2 demonstrates complex, lineage-specific outcomes in somatic stem cell systems.

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