NEURAL CREST CELL DIVERSIFICATION

描述：(摘自申请者的摘要)：胚胎细胞群体 在适当的时间、在准确的位置和 正确的数字是发育生物学的中心问题。的目标是 申请者的实验室将了解其背后的机制 在神经脊发育过程中。为了做到这一点，我们提供了一些有益的方法 利用斑马鱼和禽类胚胎独特的实验优势 将被应用于神经峰细胞命运何时以及如何的问题 在发育过程中指定，以及指定细胞的发育如何 受监管的。 这个应用程序的主要目标是识别命运受限细胞 神经脊发育初期存在的亚群 并阐明差异调节它们发育的机制。二 将采用不同的实验方法。首先，使用克隆分析 用于存在的非重叠细胞子集的技术和分子标记 在鸟类细胞培养中的初始神经脊群，它将被确定 特定分子的表达是否可作为后续细胞的诊断指标 命运。由于假定的诊断分子是生长因子受体和 它们的生长因子配体的活性可以选择性地控制在 体外，这些生长因子在受体发育中的作用 表达细胞将被确定。第二种方法利用基因突变 斑马鱼是已知的专门影响神经源性发育的 神经脊细胞。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 根据突变胚胎的表型，我们知道这两个基因都是 是神经脊发育过程中神经发生所必需的。通过比较神经 突变型和野生型胚胎的顶峰发育，正常的作用 在神经脊发育过程中由突变定义的基因将是 阐明，识别基因的第一步就完成了。

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.