| Description |
Cell migration is essential for proper vertebrate development, including the development of numerous structures derived from embryonic neural crest cells (NCCs). Although the migratory pathways of NCCs have been identified, the cellular and molecular mechanisms regulating NCCs motility remain unclear. The studies in this dissertation investigate and characterize neural crest motility in vitro on two extracellular matrix (ECM) proteins, laminin and fibronectin, as well as two cellular and molecular mechanism used by these cells, receptor recycling and integrin activation. We address three fundamental questions regarding the mechanism responsible for the extensive migration of NCCs throughout the developing embryo. First, like their immediate embryonic descendents, can NCCs migrate equally well across of range of ECM protein concentrations? Second, how do NCCs regulate their adhesion levels in order to migrate efficiently in diverse environments? And third, are the same mechanism used to promote motility of different ECM proteins? We find two subpopulations of NCCs, cranial and trunk, migrate efficiently across a wide range of laminin and fibronection concentrations by modulating both the number of cell surface adhesion receptors and their functional state. Both cranial and trunk NCCs regulate surface integrin levels in response to the concentration of laminin present in the substratum, however, cranial NCCs regulate a particular receptor, integrin ?6, to a greater degree than do trunk NCCs. Cranial NCCs rapidly internalize and recycle integrin ?6 on high laminin, and blocking receptor trafficking slows cranial NCC motility on laminin in a concentration-dependent manner. These results indicate that inhibition of receptor recycling affects the motility only of rapidly migrating NCCs, whose surface receptor expression levels are low and tightly regulated. Activation of surface integrins show cranial and trunk NCC motility of fibronection but not on laminin, and leads to distinct adhesion formation on each substrata, indicating that, in addition of substratum density, substratum composition also plays an important role in regulated NCC motility. These results demonstrate that NCCs can accommodate diverse environments in vitro and suggest that differences in integrin regulation along the anterior-posterior axis may contribute to differences in neural crest migration and cell fate. |
