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Mechanisms of junctional actin organization in epidermal morphogenesis and homeostasis

Subject Area Cell Biology
Term from 2015 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 273724076
 
The skin epidermis is a self-renewing stratifying epithelium and crucial for skin barrier function. Basal epidermal stem cells balance selfrenewal with a spatiotemporal controlled differentiation program of their progeny that is accompanied by spatial coordinated cell shape changes. However, whether these shape changes control positioning and cell fate is not clear. The classical cadherins couple intercellular adhesion to the force generating actomyosin cytoskeleton in specialized adherens junctions (AJs). These junctions thus allow cells to communicate forces across cells to coordinate cell shape changes and cellular responses. In the previous period of this SPP we identified E-cadherin in AJs as a force sensing and transducing protein that coordinates signaling and mechanical responses to regulate initial epidermal differentiation steps as well as final barrier formation. E-cadherin does so by tissue polarization of different AJ mechanical states and differential cortical actin network organization. The overall goal of the next SPP period is to determine how AJs control different states of F-actin organization and ask whether and how these states integrate cell position with cell fate and function. Together, the experiments proposed will likely contribute to a better understanding of the molecular mechanisms by which cadherin/catenin biomechanical signaling control the morphogenesis and homeostasis of stratifying epithelia.
DFG Programme Priority Programmes
 
 

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