Central to study of development is understanding how morphogenetic movements are regulated. This question has special bearing for the vertebrate neural crest, a multipotent population of cells that famously migrate in collective streams from the dorsal neural tube along conserved pathways during development. While much current theory focuses on cell autonomous factors regulating neural crest cell state, neural crest cell (NCC) migration is also known to require interactions and integration across different tissues. The overarching goal of this project is to understand how NCCs integrate internal cell state with external signals from the local cellular environment to coordinate directed migration. The proposed research will study this problem in zebrafish where trunk NCC migration depends critically on a population of somitic mesoderm called adaxial cells. Loss of adaxial cells results in NCC phenotypes suggestive of cell polarity and adhesion defects. Remarkably, adaxial cells also migrate during development, and NCC migration may be related to adaxial cell migration. Despite the importance of adaxial cells for NCC migration, the mechanisms underlying this interaction are unknown. The propose research will test the hypothesis that NCCs require adaxial cells for regulation of cell polarity, and that that this interaction is mediated through modifications to the extracellular matrix that occurs during adaxial cell migration. These data will provide insight into a regulatory mechanism controlling zebrafish NCC migration, a major morphogenetic event that occurs in every vertebrate embryo.
The overarching goal of this project is to understand how neural crest cells (NCCs) integrate internal cell state with external signals from the local cellular environment to coordinate a major cell migration event. NCCs contribute to numerous traits, and understanding how NCCs regulate migration is central to understanding the etiology of multiple hereditary disorders as well as fundamental mechanisms that guide this cell migratory event during normal development. Further, these data will inform our understanding of how cells migrate in an in vivo context more generally, and thus has implications for our understanding of the molecular control of other cell migratory events during development as well as cancer metastasis.
