Evolution of embryonic polarity: The role of the Wnt signaling pathways

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The evolution of developmental mechanisms that led to the origin of germ layers is an important unsolved question. Insight into this question will come from understanding germ layer segregation in ancient animals such as cnidarians. The PI has been using the cnidarian Nematostella vectensis to gain insight into germ layer evolution by studying the specification and evolution of the animal-vegetal (AV) axis, a fundamental polarity found in most animal eggs. Developmental information asymmetrically distributed along this axis is crucial for germ layer segregation in many species, but its molecular basis is poorly understood. The PI has shown that in Nematostella, germ layer segregation is mediated by selective activation of the evolutionarily conserved Wnt/beta-catenin pathway in animal pole-derived blastomeres. The PI has also shown that the activation of canonical Wnt signaling in future endoderm is mediated by the Dishevelled (Dsh) protein, which is localized to the egg's animal pole. During embryogenesis Dsh mRNA is expressed globally but the protein is enriched in endoderm by its selective destabilization in ectoderm. Understanding how Dsh is regulated in Nematostella eggs and embryos may provide insight into mechanisms that led to evolution of the AV axis and the germ layers. In this research, the PI will use functional molecular approaches to elucidate 1) the molecular mechanisms that restrict Dsh activation and stability to endodermal cells in Nematostella; 2) determine if Dsh regulates gut morphogenesis during development and 3) determine if Strabismus, which has been shown to antagonize canonical Wnt signaling in vertebrates, and is localized in Nematostella eggs has a role in restricting Dsh activity to endoderm. Together, these studies are likely to provide insight into one of the most mysterious events in animal evolution. The proposed work will involve graduate and undergraduate students from groups under-represented in science, and results of this research will be incorporated into graduate and undergraduate classes taught by the PI