| Epithelial to mesenchymal transition (EMT) is a dynamic process in which a cell converts from a non-migratory, epithelial phenotype to a migratory, mesenchymal phenotype and involves coordinated changes is cell polarity, adhesions, and behavior. EMTs are important for embryonic development, but also drive pathologies including cancer progression, invasion, and metastasis. Given the significance of EMT in development and disease, it is important to advance our understanding of the biology of EMT, and because the environment has a great effect on cell signaling and behavior, it is critical to examine EMT in the intact in vivo environment. Neural crest cells (NCCs) undergo EMT to initiate migration from the developing neural tube during development. Zebrafish NCCs are a tractable system in which cells can be labeled, migratory behaviors identified, and changes in these behaviors monitored after manipulation of specific molecules, making them ideal for the study of EMT in vivo. In this dissertation, I use live imaging to identify motile cell behaviors that promote NCC EMT and combine imaging with molecular manipulations to identify how specific molecules control these behaviors. In Chapter 2 I identify behaviors associated with NCC motility during EMT and identify Rho Kinase as a molecule necessary for one of these behaviors. Next, in Chapter 3 I show that the GTPase Rho is activated in specific portions of the cell during EMT, and that activation of Rho in these areas is critical for EMT. Finally, in Chapter 4 I show that Cadherin-6 drives EMT by regulating the subcellular distribution of active Rho and F-actin. Together, this work identifies a network of molecules acting to pattern signals that control cell behaviors essential for NCC EMT. |
