Mechanical instability of adherens junctions overrides intrinsic quiescence of hair follicle stem cells

Dev Cell. 2021 Mar 22;56(6):761-780.e7. doi: 10.1016/j.devcel.2021.02.020. Epub 2021 Mar 15.


Vinculin, a mechanotransducer associated with both adherens junctions (AJs) and focal adhesions (FAs), plays a central role in force transmission through cell-cell and cell-substratum contacts. We generated the conditional knockout (cKO) of vinculin in murine skin that results in the loss of bulge stem cell (BuSC) quiescence and promotes continual cycling of the hair follicles. Surprisingly, we find that the AJs in vinculin cKO cells are mechanically weak and impaired in force generation despite increased junctional expression of E-cadherin and α-catenin. Mechanistically, we demonstrate that vinculin functions by keeping α-catenin in a stretched/open conformation, which in turn regulates the retention of YAP1, another potent mechanotransducer and regulator of cell proliferation, at the AJs. Altogether, our data provide mechanistic insights into the hitherto-unexplored regulatory link between the mechanical stability of cell junctions and contact-inhibition-mediated maintenance of BuSC quiescence.

Keywords: YAP1; adherens junctions; contact inhibition; hair follicle stem cells; mechanical forces; quiescence; stretched/open α-catenin; vinculin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adherens Junctions / physiology*
  • Animals
  • Cell Adhesion
  • Female
  • Hair Follicle / cytology
  • Hair Follicle / physiology*
  • Male
  • Mechanotransduction, Cellular*
  • Membrane Potentials
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Vinculin / physiology*
  • YAP-Signaling Proteins
  • alpha Catenin / genetics
  • alpha Catenin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Ctnna1 protein, mouse
  • Vcl protein, mouse
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • alpha Catenin
  • Vinculin