The role of proteases in embryonic neural crest cells

As the embryo develops, multiple cellular events of division, differentiation, migration, and invasion occur. Cells are formed at specific locations and migrate along different axes to various destinations, by acquiring diverse types of molecular machineries and processes. One such process is the epithelial-to-mesenchymal transition (EMT), in which epithelial cells with highly ordered shapes and contacts transform into mesenchyme in order to start migration. Consequently, these separated cells react to intracellular and extracellular signals to travel through different microenvironments along stereotypical, long-distance migratory routes to their precise homing targets. Different types of proteases are necessary to execute such complex events. One excellent system to evaluate cell movements during embryonic development is the population of neural crest cells. These unique cells are initially formed as part of the neural epithelium, but then they undergo a dramatic EMT after which they extensively migrate and differentiate into various fates including craniofacial skeleton, skin pigments, and peripheral nerves. In this review, we will discuss the central roles of proteases, mainly the family of matrix metalloproteases, in facilitating neural crest cell migration, and propose an integrative model to suggest the orchestrated action of two such proteases in these developmental events.