Dynamic control of the actin cytoskeleton during convergent extension of the vertebrate embryo



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Tissue morphogenesis requires specific signaling pathways to govern precise behavior of individual cells and the collective tissue. This is exemplified by the requirement of Planar Cell Polarity (PCP) signaling to govern convergent extension (CE) and tissue elongation in model organisms and humans. During this collective cell movement, cells must rapidly rearrange the cytoskeleton, establish anteroposterior polarity, and intercalate between one another. Despite their importance during CE, how PCP proteins function during this dynamic process remains unclear. Importantly, PCP proteins and actin regulators have overlapping functions during this process, and the overarching goal of my thesis was to understand how PCP proteins interact with the cytoskeleton to govern CE. My first project defined the in vivo interactome of Cofilin during CE, identified a role for it’s cofactor Twinfilin in CE, and laid the groundwork for further mechanistic studies of actin turnover during Xenopus convergent extension (Chapter 2). In parallel, I investigated the localization of PCP proteins, found anterior PCP proteins tightly associate with and are required to remodel the actin cytoskeleton into actin rich node-and-cable structures, forming a planar polarized stiffness gradient during cell intercalations (Chapter 3). And through collaboration with the Marcotte lab, we have defined the interactome of 2 polarity proteins, Vangl2 and Dishevelled2, during CE, and identified interactions between PCP proteins and the cytoskeleton, among other things (Chapter 4). Together, by combining tissue-specific proteomics and advanced imaging approaches we have furthered our understanding of the molecular processes governing cellular movements in CE and provided new insights into the basic biology of vertebrate development.


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