Molecular analysis of neural crest migration

描述（由申请人提供）：神经嵴是一个短暂的细胞群，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迁移，沿着沿着精确的路径迁移，并最终定位在胚胎的特征部位，以形成周围神经系统的神经节，以及黑素细胞和颅面骨骼。它们形成自主神经系统，支配许多器官，如肠道，肾脏和胰腺。正确的迁移和神经支配这些目标是必要的适当的身体功能和稳态。在上一个赠款期间，我们发现，神经嵴迁移的主导指导线索可能是抑制性的：Eph受体神经嵴细胞和ephrin在尾部体节的结果在一个节段性限制迁移模式的躯干之间的相互作用。此外，表达的Slit化学排斥剂防止躯干神经嵴细胞侵入肠道（deBellard等人，2003年）。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新的候选基因，可能在迁移过程中发挥作用。在神经褶皱中鉴定的基因包括Slit、层粘连蛋白a5以及一种新的趋化因子。拟议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查：1。Slit的双重抑制和迁移刺激活性在躯干和颅神经嵴细胞迁移中的作用。 2.层粘连蛋白a5亚单位在早期神经嵴发育中的作用。 3.一种新型趋化因子在神经嵴迁移中的作用。4.这种新型趋化因子在肢体发育中的功能。

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.