REGULATION OF NEURAL CREST CELL MIGRATION BY SDF1-CXCR4 SIGNALING

SDF1-CXCR4 信号传导对神经嵴细胞迁移的调节

• 批准号: 8360172
• 负责人: Ratnam Sathiagana Seelan
• 金额: $ 10.37万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360172
• 关键词: Address; Adrenal Glands; Affect; Antibodies; BMP4; Biological Models; CXCL12 gene; CXCR4 gene; Chick Embryo; Chickens; Defect; Development; Embryo; Embryonic Development; Funding; Gene Expression Profiling; Genes; Goals; Grant; In Situ Hybridization; Mediating; Molecular; National Center for Research Resources; Neural Crest; Neural Crest Cell; PC12 Cells; Pattern; Perinatal; Peripheral Nervous System; Phosphotransferases; Principal Investigator; Process; Regulation; Research; Research Infrastructure; Resources; Signal Transduction; Source; Spinal Ganglia; Staging; Stromal Cell-Derived Factor 1; United States National Institutes of Health; cell motility; cost; islet; migration; research study; spatiotemporal

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall goal of the project is to examine if the migration of trunk neural crest cells (NCCs) to the Dorsal Root Ganglion (DRG) involves SDF1/CXCR4 signaling and to identify regulatory factors that mediate this process. Defective migration of trunk NCCs can cause perinatal lethality and affect the development and formation of the peripheral nervous system. Towards this end, we generated chicken SDF1 and CXCR4 riboprobes, and utilized them in in situ hybridization (ISH) analyses to determine the spatiotemporal expression of the two genes during embryonic development. The hypothesis being addressed is that trunk NCCs express CXCR4 and migrate towards mesodermal regions of high SDF-1 concentration where they differentiate into the DRG. Chicken embryos (Hamilton-Hamburger (HH) stages ~7 to 22) were used for the study as their developmental stages are well defined and are more amenable to analysis and manipulation. Gene expression profiling of SDF1 and CXCR4 spanning these developmental stages in the chick embryo has largely been accomplished. Using specific antibodies (anti-HNK-1 for NCCs and anti-Islet-1 for the DRG), we are now determining if the expression patterns of CXCR4 and SDF-1 correspond to the developmental paths undertaken by migrating NCCs to become DRG. To identify factors regulating NCC migration via SDF1/ CXCR4 signaling (e.g., TGF¿1 and BMP4) and the effect of this signaling on putative downstream targets, such as IP3 kinase, PC12 cells (derived from the adrenal gland and of neural crest origin) are being used as a model system in experiments employing transwells.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目的总体目标是检查躯干神经嵴细胞（NCC）迁移到背根神经节（DRG）是否涉及SDF 1/CXCR 4信号传导，并确定介导这一过程的调节因子。躯干NCC迁移缺陷可导致围产期死亡，并影响周围神经系统的发育和形成。为此，我们产生了鸡SDF 1和CXCR 4核糖核酸探针，并利用它们在原位杂交（ISH）分析，以确定这两个基因在胚胎发育过程中的时空表达。提出的假设是，躯干NCC表达CXCR 4并向高SDF-1浓度的中胚层区域迁移，在那里它们分化成DRG。鸡胚胎（Hamilton-Hamburger（HH）阶段~7至22）用于研究，因为它们的发育阶段已明确定义，更易于分析和操作。跨越鸡胚这些发育阶段的SDF 1和CXCR 4基因表达谱已基本完成。使用特异性抗体（NCC的抗HNK-1抗体和DRG的抗Islet-1抗体），我们现在确定CXCR 4和SDF-1的表达模式是否与迁移NCC成为DRG的发育路径相对应。为了鉴定通过SDF 1/CXCR 4信号传导调节NCC迁移的因素（例如，转化生长因子1和BMP 4）以及这种信号传导对推定的下游靶点（例如IP 3激酶）的作用，PC 12细胞（源自肾上腺和神经嵴来源）在采用transwell的实验中被用作模型系统。