Dissecting the Roles of Polycomb Repressive Complex 2 Subunits in the Control of Skin Development
| Autor: | Víctor Valdés, Francis J. Santoriello, Carolina N. Perdigoto, Elena Ezhkova, K. Dauber, Idan Cohen |
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| Rok vydání: | 2016 |
| Předmět: |
Keratinocytes
0301 basic medicine Somatic cell Protein subunit Polycomb-Group Proteins macromolecular substances Dermatology Biology Biochemistry Article 03 medical and health sciences Conditional gene knockout medicine Humans Enhancer of Zeste Homolog 2 Protein Molecular Biology Gene knockout Skin integumentary system Polycomb Repressive Complex 2 Cell Biology Molecular biology Embryonic stem cell Repressor Proteins 030104 developmental biology medicine.anatomical_structure Stem cell Merkel cell Hair Follicle Adult stem cell |
| Zdroj: | Journal of Investigative Dermatology. 136:1647-1655 |
| ISSN: | 0022-202X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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