Uncovering New Roles for the Cell Surface Protease ADAM13 in Neural Crest Migration

ADAMs are a family of transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. They play a variety of roles in diverse tissue types during development and can affect cell processes such as migration, differentiation, growth and survival. In the embryo, several ADAMs have proven to be integral components of the cranial of neural crest (CNC), which is a multipotent population of cells that gives rise to multiple structures of the face and head. These cells are highly motile and undergo a large-scale migration throughout the embryo that is essential for proper craniofacial development. The focus of this thesis is to better understand the role of specific ADAMs during CNC migration and how their activity is regulated. At least three ADAMs, ADAM9, 13 and 19, have been shown to participate in CNC cell migration. The work presented in this thesis demonstrates that ADAMs play a more diverse role in cell migration than previously thought. In addition to cleaving molecules on the surface of CNC cells, the results in this thesis show that ADAMs can also perform significant intracellular functions such as regulating gene expression. This thesis also explores the extracellular functions of ADAM13 in more detail, and more specifically, how cleavage of the cell adhesion molecule cadherin-11 stimulates CNC migration