Molecular analysis of neural crest migration

神经嵴迁移的分子分析

• 批准号: 6819354
• 负责人: Marianne Bronner
• 金额: $ 37.46万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6819354
• 关键词: antisense nucleic acid; cell cell interaction; cell differentiation; cell migration; chemokine; chemotaxis; chick embryo; developmental genetics; developmental neurobiology; embryo /fetus tissue /cell culture; embryogenesis; ephrins; genetically modified animals; laboratory mouse; laminin; neural crest; neurogenesis; oligonucleotides; transfection; vertebrate embryology

DESCRIPTION (provided by applicant): The neural crest is a transient population of cells, named because it arises on the "crest" of the closing neural tube. Neural crest cells emigrate from the neural tube, migrate along precise pathways and finally localize in characteristic sites in the embryo to form the ganglia of the peripheral nervous system, as well as melanocytes and the craniofacial skeleton. They form the autonomic nervous system that innervates numerous organs such as the gut, kidneys and pancreas. Correct migration to and innervation of these targets is essential for proper body function and homeostasis. During the previous grant period, we showed that the dominant guidance cues for neural crest migration may be inhibitory: interactions between Eph receptors on neural crest cells and ephrins in the caudal somite results in a segmentally restricted migratory pattern in the trunk. In addition, Slit chemorepellants expressed prevent trunk neural crest cells from invading the gut (deBellard et al., 2003). Using a genomics approach, we have analyzed the repertoire of genes expressed by premigratory neural crest cells. This has provided us with numerous new candidate genes that may function in the migratory process. Genes identified in neural folds include Slit, laminin a5, as well as a novel chemokine. The proposed experiments will characterize the function of these candidate genes in regulating important events in neural crest migration and other developmental processes. We will use both in vivo and in vitro experiments combining gain-of-function and loss-of-function approaches to examine: 1. The role of the dual inhibitory and migration-stimulating activity of Slit in the migration of trunk and cranial neural crest cells. 2. The function of the a5 subunit of laminin in early neural crest development. 3. The function of a novel chemokine in neural crest migration. 4. The function of this novel chemokine in limb development.

描述（由申请人提供）：神经嵴是一种短暂的细胞群，命名是因为它出现在闭合神经管的“嵴”上。神经嵴细胞从神经管中迁移，沿着精确的路径迁移，最终定位于胚胎的特征部位，形成周围神经系统的神经节，以及黑色素细胞和颅面骨骼。它们形成自主神经系统，支配许多器官，如肠道、肾脏和胰腺。这些目标的正确迁移和神经支配对正常的身体功能和体内平衡至关重要。在之前的研究期间，我们发现神经嵴迁移的主要引导线索可能是抑制性的：神经嵴细胞上的Eph受体与尾状体中ephrin的相互作用导致主干的节段性限制迁移模式。此外，表达的狭缝化学排斥剂可以防止主干神经嵴细胞入侵肠道（deBellard等，2003）。使用基因组学方法，我们分析了迁移前神经嵴细胞表达的基因库。这为我们提供了许多可能在迁移过程中起作用的新候选基因。在神经折叠中发现的基因包括Slit，层粘连蛋白a5，以及一种新的趋化因子。提出的实验将表征这些候选基因在调节神经嵴迁移和其他发育过程中的重要事件中的功能。我们将使用体内和体外实验结合功能获得和功能丧失的方法来检验：Slit在主干和颅神经嵴细胞迁移中的双重抑制和刺激作用。