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Abstract

Epithelial morphogenesis consists of the various process that promote the bending, folding, and rearrangement of tissues during organ formation and development. At the heart of these processes, complex organizations and contractions of the actomyosin cytoskeleton drive the individual cell shape changes that underlie tissue morphogenesis. The assembly and dynamics of these actomyosin networks are regulated by a host of actin-binding proteins, as well as regulatory molecules such as the RhoA Family of GTPases. Although much is known about the structure and function of the individual components of contractile networks, much less is known about how cells tune the organization and dynamics these networks in space and in time. The subject of this thesis is one mode of contractility known as pulsed contractility. Pulsed contractions have been shown to be a key regulator in various instances of tissue morphogenesis. We have shown that autocatalytic activation of active RhoA drives pulsed contractions in the early \textit{C.elegans} embryo. The accumulation of active RhoA precedes the activation, assembly, and recruitment of F-actin, Myosin II, and Anillin within pulsed contractions. We have also shown that pulses of active RhoA do not depend on the presence of Myosin II or Anillin. The delayed accumulation of the redundant RhoA GAPs RGA-3 and RGA-4 relative to active RhoA, and the loss of active RhoA pulses in \textit{rga-3/4} mutants, is consistent with RGA-3/4-mediated negative feedback terminating RhoA pulses. The fact that GFP::RGA-3 strongly co-localizes with F-actin, and the depolymerization of F-actin leads to a near-total loss of GFP::RGA-3 on the cortex and global activation of RhoA, suggests that F-actin mediates this negative feedback. We believe that the results presented here lay the foundation for a novel conceptual framework, in which the spatial and temporal kinetics of RhoA activations is tightly coupled to the dynamics of the underlying actomyosin cytoskeleton.

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