TY - JOUR
T1 - Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development
AU - Dauber, Katherine L.
AU - Perdigoto, Carolina N.
AU - Valdes, Victor J.
AU - Santoriello, Francis J.
AU - Cohen, Idan
AU - Ezhkova, Elena
N1 - Funding Information:
We would like to thank Evan Bardot, Jose Silva, Julie Segre, and Elaine Fuchs for help, advice, critical suggestions, experimental input, and reagents,. We would also like to thank Weipeng Mu and Terry Magnuson for their generous gift of the Suz12 floxed and EED floxed mice ( Mu et al., 2014 ). The Ezh1 mutant mice were generated at the Research Institute of Molecular Pathology (IMP, Vienna, Austria) by Donal O'Carroll (laboratory of Thomas Jenuwein) with the help of Maria Sibilia (laboratory of Erwin Wagner). We would like to thank Alexander Tarakhovsky for previously providing us with Ezh2 floxed mice. Microscopy was performed at the Microscopy CORE at the Icahn School of Medicine at Mount Sinai. KLD is a trainee of the NIDCR-Interdisciplinary Training Program in Systems and Developmental Biology and Birth Defects T32HD075735. CNP was supported by EMBO fellowship ALTF 552-2012. VJV is a Pew Latin American Fellow in the Biomedical Sciences, supported by The Pew Charitable Trusts. EE is an Ellison Medical Foundation New Scholar in Aging. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01 AR063724 and R01 AR069078. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by a New York State Stem Cell Science (NYSTEM) IDEA grant through New York State Department of Health (N11G-152).
Publisher Copyright:
© 2016 The Authors
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84992482151&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2016.02.809
DO - 10.1016/j.jid.2016.02.809
M3 - Article
C2 - 26994968
AN - SCOPUS:84992482151
VL - 136
SP - 1647
EP - 1655
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 8
ER -