Evolutionary divergences of cadherin-mediated cell contacts and their impacts on morphogenesis

Objective

As a zygote develops into a multicellular organism, cell contacts are crucial to shape the embryo. Metazoans utilize Cadherin proteins for adhesion in which the extracellular domains establish cell contacts and intracellular domains mechanically couple the cytoskeleton. The nature of the cell contact is critical for defining cell shapes and the physical properties of the tissue. While the intracellular domain is highly conserved, the architecture of their extracellular domains varies widely across species. How these differences influence cell contacts at the microscale and morphogenesis at the macroscale remains largely unexplored. In this study, I will conduct a comparative analysis of cell contacts using widely diverse Cadherin extracellular domains from vertebrates, cephalochordates, arthropods, and cnidarians. I will express these exogenous Cadherins in zebrafish embryos and test their impacts on cell contacts at three levels. First, I will characterize Cadherin-mediated contacts at the single-cell level using biomimetic supported lipid bilayers. Second, I will quantify adhesion strength and cell contact dynamics in cell doublets. Finally, I will assess how different Cadherins influence morphogenetic movements at the tissue level in zebrafish development. Together, this work will uncover fundamental principles of Cadherin extracellular domain evolution and its impact on cell adhesion. In this work, I will develop tools to carry out comparative analyses of cell adhesion which can potentially be transferred to other organisms. This work will help bridge the gap between molecular evolution, cell mechanics, and large-scale morphogenetic processes, revealing how evolution may utilize adhesion mechanisms to drive the diversity of life forms.