The Roles of the Planar Cell Polarity Molecules Prickle1a and Prickle1b in Zebrafish Cranial Neural Crest

In this dissertation, I will discuss my investigation into the roles of two molecules, zebrafish Prickle1b and Prickle1a, part of a suite of proteins called Planar Cell Polarity (PCP) proteins, in the specific context of a multipotent stem cell population, the neural crest. Neural crest cells have been likened to metastatic cancer cells in how they invade regions of the developing embryo by traversing large distances and subsequently differentiating into many different cell types. PCP proteins are known to behave in a variety of different contexts in both Drosophila melanogaster and vertebrate model systems, and although two other PCP proteins have been investigated in the cranial sub-population of the migrating neural crest in vertebrates, this is the first investigation into the roles of the pk1 paralogous genes, or any PCP genes, broadly during neural crest development including well before crest cells begin their migration. I demonstrate that not only are zebrafish Pk1b and Pk1a required for cranial neural crest migration, they are additionally required in a process that precedes migration: an epithelial-to-mesenchymal transition (EMT) that occurs in neural crest cells and many other cell types in both vertebrate and invertebrate developing embryos. EMT allows neuroepithelial cells within the developing neural tube to transition to cells that lie outside the neural tube and eventually migrate away to different locations in developing embryos. By showing that the zebrafish PCP Pk1 proteins regulate specific morphological transitions during EMT that are required for neural crest cells to migrate away from their initial location, as well as during migration itself, at least partly through the regulation of the levels of two members of the Cadherin-family of adhesion molecules, I demonstrate roles for the PCP Pk1 molecules broadly during neural crest development through a hitherto-unrecognized function of PCP signaling during the process of EMT.