Seminars

Anchoredcells of the basal epidermis constantly undergo proliferation in an overcrowdedenvironment. One important regulator of epidermal proliferation is YAP, whichcan be controlled by both cell-matrix and cell-cell interactions. During myPh.D., I discovered that Thy1, a GPI anchored protein, inhibits epidermal YAPactivity through converging molecular mechanisms. We found that Thy1 deficiencyleads to increased adhesion by activating the Integrin-β1/Srcmodule. Notably, regardless of high cellular densities, the absence of Thy1leads to the dissociation of an adherensjunction complex that enables the release and translocation of YAP. Due toincreased YAP-dependent proliferation, Thy1-/-micedisplay enhanced wound repair and YAP-dependent hair follicle regeneration.Taken together, our work reveals Thy1 as a critical regulator of cell-matrixand cell-cell interactions that controls YAP activity in skin homeostasis,regeneration and tumorigenesis.