Yap Controls Stem/Progenitor Cell Proliferation in the Mouse Postnatal Epidermis

被引:61
作者
Beverdam, Annemiek [1 ]
Claxton, Christina [1 ]
Zhang, Xiaomeng [2 ,3 ,4 ]
James, Gregory [1 ]
Harvey, Kieran F. [2 ,3 ,4 ]
Key, Brian [1 ]
机构
[1] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia
[2] Peter MacCallum Canc Ctr, Cell Growth & Proliferat Lab, East Melbourne, Vic, Australia
[3] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia
[4] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia
基金
英国医学研究理事会;
关键词
YES-ASSOCIATED PROTEIN; HAIR FOLLICLE MORPHOGENESIS; HIPPO PATHWAY; BETA-CATENIN; ORGAN SIZE; TRANSCRIPTIONAL COACTIVATOR; TRANSIENT ACTIVATION; CONTACT INHIBITION; TEAD/TEF FAMILY; STEM-CELLS;
D O I
10.1038/jid.2012.430
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Tissue renewal is an ongoing process in the epithelium of the skin. We have begun to examine the genetic mechanisms that control stem/progenitor cell activation in the postnatal epidermis. The conserved Hippo pathway regulates stem cell turnover in arthropods through to vertebrates. Here we show that its downstream effector, yes-associated protein (YAP), is active in the stem/progenitor cells of the postnatal epidermis. Overexpression of a C-terminally truncated YAP mutant in the basal epidermis of transgenic mice caused marked expansion of epidermal stem/progenitor cell populations. Our data suggest that the C-terminus of YAP controls the balance between stem/progenitor cell proliferation and differentiation in the postnatal interfollicular epidermis. We conclude that YAP functions as a molecular switch of stem/progenitor cell activation in the epidermis. Moreover, our results highlight YAP as a possible therapeutic target for diseases such as skin cancer, psoriasis, and epidermolysis bullosa.
引用
收藏
页码:1497 / 1505
页数:9
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