Cell migration is an integral biological mechanism involved in many biological processes including immune response and tissue homeostasis, and is required for the proper shaping of organs and tissues during animal development. Aberrant cell migration can result in various developmental disorders including cleft palate syndrome, and in the development of chronic inflammation. Moreover, aberrant cell migration represents the basic mechanism for the formation of metastases in cancer. The neural crest is a stem-cell like population that arises at the border between the neural tube and epidermis and gives rise to a number of different cell types. Proper cell migration from the neural crest in the early embryo is required for the normal differentiation of multiple cell types such as neurons, pigment cells and Craniofacial cartilage. An important question is how cell migration is initiated and regulated in response to both genetic and environmental cues in the appropriate cells. To address this question, I propose to study neural crest cell migration in zebrafish using the prdml mutant, which displays aberrant trunk neural crest cell migration. I will first characterize the behavior of wild type and prdml mutant neural crest cells using live flourescence imaging. I then plan to carry out thorough genetic, molecular, and biochemical analyses of the behavior and regulation of neural crest cell migration using the prdml mutant. I will also examine the potential roles of other candidate genes in regulating cell migration within the neural crest. Given that cell migration is a common and highly conserved mechanism, this research has the potential to provide insight into how cell migration is regulated in humans. Such insight may prove beneficial to clinical research on diseases that are caused by inappropriate cell migration such as in a variety of developmental disorders and specifically in the development of metastases in cancer.
