Oral Presentation 6th Australian Health and Medical Research Congress 2012

Yap controls stem/progenitor cell proliferation in the mouse postnatal epidermis  (#124)

Annemiek Beverdam 1 , Christina Claxton 1 , Xiaomeng Zhang 2 3 4 , Gregory James 1 , Kieran Harvey 2 3 4 , Brian Key 1
  1. School for Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
  2. Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  3. Sir Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  4. Department of Pathology, University Melbourne, Melbourne, VIC, Australia

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 turn over in arthropods through to vertebrates. We show here 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 protein mutant in the basal epidermis of transgenic mice caused dramatic 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.

(Accepted for publication in Journal of Investigative Dermatology)