title: Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development.
abstract: Polycomb repressive complex 2 (PRC2) is an essential regulator of cell physiology. Although there have been numerous studies on PRC2 function in somatic tissue development and stem cell control, these have focused on the loss of a single PRC2 subunit. Recent studies, however, have shown that PRC2 subunits may function independently of the PRC2 complex. To investigate the function of PRC2 in the control of skin development, we generated and analyzed three conditional knockout mouse lines, in which the essential PRC2 subunits embryonic ectoderm development (EED), suppressor of zeste 12 homolog (Suz12), and enhancer of zeste homologs 1 and 2 (Ezh1/2) are conditionally ablated in the embryonic epidermal progenitors that give rise to the epidermis, hair follicles, and Merkel cells. Our studies showed that the observed loss-of-function phenotypes are shared between the three knockouts, indicating that in the skin epithelium, EED, Suz12, and Ezh1/2 function largely as subunits of the PRC2 complex. Interestingly, the absence of PRC2 results in dramatically different phenotypes across the different skin lineages: premature acquisition of a functional epidermal barrier, formation of ectopic Merkel cells, and defective postnatal development of hair follicles. The strikingly different roles of PRC2 in the formation of three lineages exemplify the complex outcomes that the lack of PRC2 can have in a somatic stem cell system.
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Dauber
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Carolina N
authors.initials: CN
authors.lastname: Perdigoto
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Valdes
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Santoriello
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Idan
authors.initials: I
authors.lastname: Cohen
authors.affiliation: Black Family Stem Cell Institute, Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: elena.ezhkova@mssm.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Ezhkova
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002469:Cell Separation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D017404:In Situ Hybridization, Fluorescence; D018862:Merkel Cells / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D010641:Phenotype; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
chemical_list: C107275:Eed protein, mouse; C494163:Suz12 protein, mouse; D000071221:Enhancer of Zeste Homolog 2 Protein; C498408:Ezh1 protein, mouse; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2