The regulation of neural crest cell migration during zebrafish development

描述（由申请人提供）：细胞迁移是一种完整的生物机制，涉及许多生物过程，包括免疫反应和组织稳态，是动物发育过程中器官和组织正确形成所必需的。异常的细胞迁移可导致各种发育障碍，包括腭裂综合征和慢性炎症的发展。此外，异常的细胞迁移是癌症转移形成的基本机制。神经嵴是一种类似干细胞的细胞群，出现在神经管和表皮之间的边界，并产生许多不同类型的细胞。胚胎早期神经嵴的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在适当的细胞中响应遗传和环境线索而启动和调节的。为了解决这个问题，我建议使用prdml突变体来研究斑马鱼神经嵴细胞的迁移，该突变体表现出异常的主干神经嵴细胞迁移。我将首先用活荧光成像来描述野生型和prdml突变型神经嵴细胞的行为。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，这项研究有可能为了解人类细胞迁移是如何调节的提供见解。这种见解可能有助于对由不适当的细胞迁移引起的疾病的临床研究，例如各种发育障碍，特别是癌症转移的发展。

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.