NEURAL CREST CELL DIVERSIFICATION

描述：（来自申请人摘要）：胚胎细胞群如何 在适当的时间，在精确的位置产生专门的细胞类型， 是发育生物学的核心问题。的目标 申请人的实验室是为了了解这些潜在的机制， 神经嵴发育过程中的突起。为了做到这一点， 利用斑马鱼和鸟类胚胎独特的实验优势， 将被应用于神经嵴细胞的命运何时以及如何 在发育过程中指定，以及指定细胞的发育如何 监管. 本申请的主要目的是识别命运限制细胞 在神经嵴发育的初始阶段出现的亚群 并阐明差异调节其发育的机制。两 将采用不同的实验方法。首先，使用克隆分析 技术和分子标记，用于存在于 在禽类细胞培养物中的初始神经嵴群体，将确定 特异性分子的表达是否是后续细胞的诊断 命运由于推定的诊断分子是生长因子受体， 它们的生长因子配体的活性可以选择性地控制 体外，这些生长因子在受体发育中的作用 将确定表达细胞。第二种方法利用了 斑马鱼，已知专门影响神经原性的发展， 神经嵴细胞因此，与第一种方法相比，分子 被突变破坏的基因的身份目前尚不清楚，但 基于突变胚胎的表型，已知这两种基因都是 是神经嵴发育过程中神经发生所必需的。通过比较神经 突变体和野生型胚胎的嵴发育， 在神经嵴发育过程中由突变定义的基因将被 阐明，并确定基因的第一步将完成。

DESCRIPTION: (from applicant's abstract): How embryonic cell populations generate specialized cell types at appropriate times, in precise locations and in correct numbers are central issues in developmental biology. The goal of the applicant's laboratory is to understand the mechanisms underlying these processes during neural crest development. To do so, complimentary approaches utilizing the unique experimental advantages of zebrafish and avian embryos will be applied to the question of when and how neural crest cell fates are specified during development, and how the development of specified cells is regulated. The main objectives of this application are to identify fate-restricted cell subpopulations present during the initial stages of neural crest development and to elucidate mechanisms that differentially regulate their development. Two distinct experimental approaches will be employed. First, using clonal analysis techniques and molecular tags for non-overlapping subsets of cells present in initial neural crest populations in avian cell cultures, it will be determined whether the expression of specific molecules are diagnostic of subsequent cell fate. Since the putative diagnostic molecules are growth factor receptors and the activity of their growth factor ligands can be selectively controlled in vitro, the role of these growth factors in the development of receptor expressing cells will be determined. The second approach utilizes mutations in zebrafish that are known to specifically affect the development of neurogenic neural crest cells. Thus, in contrast to the first approach, the molecular identities of the genes disrupted by the mutations are not presently known, but based on the phenotypes of mutant embryos, it is known that both genes are required for neurogenesis during neural crest development. By comparing neural crest development in mutant and wild type embryos, the normal roles of the genes defined by the mutations during neural crest development will be elucidated, and the first step in identifying the genes will be completed.