The Role of Formins In Regulating Multicellular Mechanics During Tissue Stratification

University Of Chicago, Chicago IL

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Abstract

? DESCRIPTION (provided by applicant): This research addresses a fundamental question in epithelial biology: What determines whether epithelial sheets exist as monolayers, like the intestine or kidney ductules, or multilayered structures like the skin and cornea? Despite an abundance of genetic data, a gap remains in our understanding of how molecular determinants physically elicit or prevent stratification. Prior work indicates that Rho-GTPases and downstream myosin contraction activators support proper stratified tissue architecture. Rho-GTPases also reshape the network upon which myosin operates by activating formins, a protein family responsible for nucleating and elongating cytoskeletal actin filaments. Nonetheless, the contribution of formin-mediated actin architecture to tissue stratification has received little attention. I hypothesize that cadherins exploit formins to ensure that cell contacts engage contractile machinery via linear actin conduits, prone to snapping, and, in turn, conducive to basal layer exit.