Zebrafish epiboly as a model of vertebrate embryonic cell rearrangement

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A major question in developmental biology is how morphogenesis, or the coordination of cell shape and cell movement, generates the correct structure of tissues and organs in all animals. We study the morphogenetic movement called epiboly which is the thinning and spreading of a sheet or multi-layer of cells. It is used widely in animal development, including in humans, and when it goes wrong, profound developmental patterning defects result. Despite its importance, the cellular and molecular basis of epiboly is not fully understood. Here we focus on the molecular and cellular mechanisms that control the process of epiboly in order to generate the adult vertebrate body plan.******This work will be conducted using the zebrafish embryo, an important vertebrate model with many advantages for this type of research. The zebrafish system provides a variety of methodologies and experimental approaches to study cell behavior and gene function, and it is ideal for analyzing morphogenesis due to the transparency of the embryo. In addition, epiboly in the zebrafish embryo occurs in parallel in three distinct tissue contexts, allowing us to study it in a cell sheet, a cell mass and a yolk cell; and to analyze the mechanical and regulatory interactions between these regions. Our objectives are to: (1) investigate the function of the Rab25 protein, which we have shown is required for normal epiboly (2) investigate the cellular basis of critical interactions between the cell sheet and the cell mass during epiboly and (3) investigate the role of the yolk cell in epiboly. ******Deepening our understanding of the mechanisms of epiboly will enhance our knowledge of animal development in general by providing insights into common cell behaviors. Importantly, by using the zebrafish model to study the same overall process in three mechanistically distinct tissue contexts, we will be able to ultimately generate a model of how distinct morphogenetic mechanisms are functionally integrated at the organismal level.