The regulation of neural crest cell migration during zebrafish development

描述（由申请人提供）：细胞迁移是许多生物学过程（包括免疫应答和组织稳态）中涉及的一种不可或缺的生物学机制，并且是动物发育期间器官和组织正确成形所必需的。异常的细胞迁移可导致各种发育障碍，包括腭裂综合征，以及慢性炎症的发展。此外，异常细胞迁移代表了癌症转移形成的基本机制。神经嵴是一个干细胞样的群体，出现在神经管和表皮之间的边界，并产生许多不同的细胞类型。早期胚胎中神经嵴的适当细胞迁移是多种细胞类型如神经元、色素细胞和颅面软骨正常分化所必需的。一个重要的问题是细胞迁移是如何启动和调节的遗传和环境的线索在适当的细胞。为了解决这个问题，我建议研究神经嵴细胞迁移在斑马鱼使用的prdml突变体，显示异常的躯干神经嵴细胞迁移。我将首先使用活体荧光成像来描述野生型和prdml突变体神经嵴细胞的行为。然后，我计划使用prdml突变体对神经嵴细胞迁移的行为和调节进行彻底的遗传、分子和生化分析。我还将研究其他候选基因在调节神经嵴内细胞迁移中的潜在作用。鉴于细胞迁移是一种常见且高度保守的机制，这项研究有可能深入了解人类细胞迁移是如何调节的。这种见解可能证明有益于对由不适当的细胞迁移引起的疾病的临床研究，例如在各种发育障碍中，特别是在癌症转移的发展中。

DESCRIPTION (provided by applicant): 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.