Mechanisms of cytoskeleton dynamics during neural crest cell chemoattraction

描述(由申请人提供)：神经脊提供了一个独特的迁移干细胞群体，用来研究各种细胞和神经发育过程。神经脊细胞在胚胎发育早期从神经管中长出，并在整个胚胎中迁移。我们才刚刚开始了解它们高运动性和不同指导下的细胞骨架变化。神经脊细胞是如何如此精确地针对特定的衍生品和身体区域的？过去20年的研究表明，趋化分子在神经脊迁移中起着至关重要的作用。然而，在神经脊细胞发育过程中化学诱导剂的存在仍然是一个有争议的问题。我们的试验资助显示，通过一套新开发的方法来研究它们的迁移，主干神经脊细胞向NRG1迁移得很厉害。有趣的是，神经脊细胞的迁移一再被比作转移和侵袭的过程。然而，尽管有大量关于控制细胞运动和侵袭过程的机制的研究，但我们没有太多证据表明神经脊细胞经历与癌细胞相似的亚细胞变化。间充质迁移细胞的一个关键步骤是细胞骨架的极化。细胞在经历了细胞骨架的特定变化后，会对趋化物质(或化学抵抗剂)做出反应(朝着)，这种变化使细胞的肌动蛋白和微管蛋白细胞骨架极化。拟议中的新实验的目标是通过研究一些改变其向定向迁移的潜在细胞骨架机制，进一步扩展我们关于NRG1对躯干神经脊细胞化学吸引的初步发现。

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.