@article{Contractile:2815,
      recid = {2815},
      author = {Cavanaugh, Kate Elizabeth},
      title = {RhoA Mediates Adaptive Junction Mechanics and Contractile  Asymmetry},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2021-03},
      pages = {172},
      abstract = {Epithelia undergo morphogenetic remodeling events to  generate the embryo’s final form. Morphogenetic episodes  may arise from relatively small, discrete changes in  cellular behaviors, namely cell migration, constriction,  intercalation, division, and extrusion events. These highly  conserved behaviors arise from the spatial and temporal  integration of cytoskeletal-based contractile forces at  adhesion complexes, the tuning of which can either maintain  tissue homeostasis or allow for dynamical tissue processes.  This mechanochemical signaling therefore underlies  mechanical force transmission and transduction necessary  for proper cell and tissue mechanics. Failure in the strict  regulation of this mechanochemical circuitry can result in  aberrant cellular and tissue behaviors, producing various  birth defects and cancers. As embryogenesis is highly  complex in nature, reductionist approaches have become  increasingly appealing and tractable to shed light on  conserved morphogenetic mechanisms. The work described here  takes a bottom-up approach to elucidate the complex  behaviors described in development. Specifically, to  examine cell shape maintenance and cell-cell junction  length regulation via the cytoskeletal regulator and small  GTPase, RhoA. RhoA is highly dynamic during morphogenesis  and exhibits complex behaviors that are thought to generate  asymmetric, ratcheted junction length changes. However,  little is known about RhoA regulation in determining  junction length and contractile phenotypes. Here, I use  optogenetic probes and various pharmacological compounds to  exogenously regulate RhoA at cell-cell junctions,  elucidating what is necessary and sufficient to drive cell  shape changes in model epithelia. I couple this work with a  collaboration in mathematical modeling to further elucidate  the mechanisms by which RhoA confers junction length.  Together, we find that junction deformation contains a  strain threshold to dictate junction length and that the  duration, strength, and temporal sequence of RhoA-mediated  contractility confers length. Junction stabilization at  shorter lengths requires endocytosis to remove junctional  and membrane material for progressive shortening. I  additionally find that, during contraction, junction  shortening occurs asymmetrically with one motile vertex and  one less-motile vertex. This vertex motion is dependent on  the feedback between RhoA and E-Cadherin, which produces an  opposing frictional force to limit junctional contractions.  The work described here begins to uncover the biophysical  and cellular basis of RhoA regulation in junction  mechanics, providing exciting new hypotheses to test how  RhoA-mediated mechanical forces drive junction length  changes. },
      url = {http://knowledge.uchicago.edu/record/2815},
      doi = {https://doi.org/10.6082/uchicago.2815},
}