Mechanisms of cytoskeleton dynamics during neural crest cell chemoattraction

California State University Northridge, Northridge CA

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Abstract

DESCRIPTION (provided by applicant): The neural crest provides a unique population of migratory stem cells with which to study a variety of cell and neural developmental processes. Neural crest cells emerge from the neural tube early in embryonic development and migrate throughout the embryo. We are just beginning to understand the cytoskeletal changes underlying their high motility and varied guidance. How do neural crest cells target particular derivatives and body regions with such precision? Research in the past 20 years has shown that chemorepellant molecules play crucial roles in neural crest migration. However, the presence of chemoattractants during neural crest cell development remained a controversial one. Our Pilot grant showed that trunk neural crest cells migrate vigorously towards NRG1 with a set of newly developed assays to study their migration. Interestingly, neural crest cell migration has been repeatedly likened to the process of metastasis and invasion. However, although there is a wealth of research on the mechanisms that govern the process of cell motility and invasion, we do not have much evidence showing that neural crest cells undergo similar sub-cellular changes as those seen in cancer cells. One critical step for mesenchymal migratory cells is the polarization of their cytoskeleton. Cells will respond (move towards) to a chemoattractant (or chemorepellant) after undergoing specific changes in their cytoskeleton that allows them to polarize their actin and tubulin cytoskeleton. The goal of the proposed new experiments is to further extend our preliminary findings on trunk neural crest cell chemoattraction by NRG1 by studying some of the underlying cytoskeletal mechanisms that change their migration towards a directional one. PUBLIC HEALTH RELEVANCE: Neural crest cell migration has been repeatedly likened to the process of metastasis and invasion. However, although there is a wealth of research on the mechanisms that govern the process of cell motility and invasion, we do not have much evidence showing that neural crest cells undergo similar sub-cellular changes as those seen in cancer cells. The proposed research will study in extensive detail the changes that trunk neural crest actin and tubulin cytoskeleton undergo (polarizing, dynamics and leading edge formation) during chemoattraction to NRG1. The outcomes from this research will help us understand how we may be able to harness the metastatic aggressiveness of crest derived-cancers because it will look into the changes that allow neural crest cells migrate throughout the embryo as it happens in adults suffering from these cancers.