A functional analysis of the evolution of metazoan cell polarity

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All living cells have polarity (e.g. front-back, top-bottom) which is absolutely essential for their normal function. For example, epithelial cells generate "inside" and "outside" barriers and embryonic cell polarity is required for cells to make important decisions on what they are going to give rise to in adult forms. Recent work has shown that many of the same molecules are used in both epithelial and embryonic cell polarity. This grant uses both comparative and functional genomics in animals with simple body plans to discover how these molecules are deployed to give rise to normal functioning tissues. By inhibiting their normal molecular interactions these findings will have important implications for how normal adult organs function (e.g. gut, heart, lung) and how disruptions/mutations in these processes give rise to birth defects. The research plan has other broader impacts such as demonstrating that many different kinds of animals and techniques are useful for understanding how life "works" and that local community members, including over 5,000 K-12 STEM students per year, will be exposed to the value of the maintaining coastal marine environments surrounding the Whitney Lab for Marine Bioscience that provide homes for the animals utilized for this research.This project tests the hypothesis that fundamental changes in the spatial deployment and interactions of molecules underlying both cellular and tissue polarity were essential for animal organ and body plan evolution. Recent discoveries showing crucial differences in the deployment of Par, cWnt, and PCP Wnt signaling pathways in embryos of the cnidarian Nematostellla vectensis relative to bilaterian species suggest that the site of gastrulation (endomesoderm formation), changed from the animal pole in ctenophores and cnidarians (i.e. "prebilaterians") to the vegetal pole in bilaterians. Furthermore, changes in the gene regulatory network that give rise to the trifunctional endomesoderm in cnidarians were responsible for the formation of distinct endodermal and mesodermal tissue types. Comparative and forward functional genomic approaches (including transgenesis, mRNA misexpression and CRISPR/Cas9 genome editing) utilizing embryos of the acoel flatworm Hofstenia miamia (a member of the earliest branching clade of triploblastic bilaterians), and the ctenophore Mnemiopsis leidyi (a metazoan clade predating the origin of cnidarians + bilaterians), both available year round at the Whitney Marine Lab, will be used to determine the sequence of molecular changes responsible for bilaterian evolutionary innovations. These studies will determine the integration between cell signaling, the cytoskeleton, and cell adhesion systems in the regulation of cell polarity during the developmental process of these two species.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.