Dr. Ashley Bruce
Department of Cell
and Systems Biology

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Zebrafish epiboly as a model of vertebrate embryonic cell rearrangement
Two primary cellular characteristics underlie changes in embryonic form; cell adhesiveness and cell motility. The strength and specificity of cell adhesions have important consequences for morphogenesis and are controlled by differential expression of cell surface proteins. Cell motility includes the ability of cells to move to new positions and change their shapes, which they do via rearrangements of the cytoskeleton. Ultimately, changes in embryonic form are under genetic control, relying upon precise spatial and temporal gene expression. In vertebrate morphogenesis, active migration of groups of cells, or collective cell migration, plays a prominent role. Examples include migration of neural crest cells and, in adult tissues, invasion of tumour cells leading to cancer metastasis. A related but distinct process is the active movement of cells across each otherís surface, variously termed cell rearrangement, cell intercalation or intercellular migration. Despite the importance of this process for normal development, the mechanisms by which cells move across each other are poorly understood.

We study epiboly, or the thinning and spreading of a multilayered cell sheet, as a model system for cell rearrangement. Epiboly is used during development in many species and when epiboly is blocked, subsequent development is severely disrupted. Despite the importance of epiboly for normal development, we know little about its cellular basis and molecular control. Our goal is to understand the cell behaviours underlying epiboly and the genetic mechanisms that control it.

Formation and function of the vertebrate organizer
Formation of the body plan requires both coordinated cellular rearrangements and patterning to establish cell and tissue fates. The organizer is essential for dorsal-ventral (DV) patterning in vertebrate embryos, demonstrated by the fact that it is capable of inducing a secondary axis when transplanted to the ventral side of a host embryo. The transplanted organizer contributes predominantly to axial mesoderm, whereas the vast majority of the secondary axis is comprised of host cells that have been re-specified from their original cell fates by signals from the transplanted organizer. Thus, a distinctive feature of the organizer is its ability to influence distant cell fates as well as to generate axial tissues. Surprisingly, investigation of the interrelationship between these short- and long-range organizer activities has not been a major research focus. It is known that many genes linked to organizer activity have highly overlapping functions, making it difficult to determine the precise functions of individual genes. Our work addresses basic questions about organizer activity, including: its short and long-range signaling functions, the extent to which the two are linked, and the mechanisms underlying the redundancy of organizer gene activity.