The regulation of neural crest cell migration during zebrafish development

描述(申请人提供)：细胞迁移是一个完整的生物学机制，涉及许多生物过程，包括免疫反应和组织动态平衡，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包括腭裂综合征在内的各种发育障碍，并导致慢性炎症的发展。此外，细胞的异常迁移是癌症转移形成的基本机制。神经脊是一种类似干细胞的群体，位于神经管和表皮的交界处，并产生许多不同类型的细胞。在胚胎早期，多种细胞如神经元、色素细胞和颅面软骨的正常分化需要适当的细胞迁移。一个重要的问题是，在适当的细胞中，细胞迁移是如何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脊细胞的迁移，该突变体显示出异常的躯干神经脊细胞迁移。我将首先使用实时荧光成像来表征野生型和prdm1突变神经脊细胞的行为。然后，我计划使用prdml突变体对神经脊细胞迁移的行为和调控进行彻底的遗传、分子和生化分析。我还将研究其他候选基因在调节神经脊内细胞迁移方面的潜在作用。鉴于细胞迁移是一种常见且高度保守的机制，这项研究有可能为深入了解细胞迁移是如何在人类中调节的。这种洞察力可能有助于对细胞不适当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.