In Vivo Analysis of the Mechanisms of Neural Crest Migration

神经嵴迁移机制的体内分析

• 批准号: 7692951
• 负责人: PAUL KULESA
• 金额: $ 33.79万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692951
• 关键词: Address; Affect; Behavior; Biological; Cardiovascular Physiology; Cardiovascular system; Cell Communication; Cell Lineage; Cells; Cellular Morphology; Cephalic; Chick Embryo; Complex; Congenital Abnormality; Cues; Data; Defect; Development; Developmental Biology; Embryo; Ensure; Enteric Nervous System; Environment; Exclusion; Goals; Image; Individual; Invaded; Knowledge; Label; Laboratories; Life; Microsurgery; Modeling; Molecular; Neural Crest; Neural Crest Cell; Neuropilins; Organ; Pathway interactions; Pattern; Peripheral; Phenotype; Play; Population; Positioning Attribute; Role; Signal Pathway; Signal Transduction; Speed; Stem cells; Stream; Structure; Subgroup; Testing; Tissue Transplantation; Translating; Vascular Endothelial Growth Factors; base; cell behavior; cell motility; cellular imaging; craniofacial; in vivo; in vivo Model; insight; migration; novel; novel therapeutics; photoactivation; prevent; public health relevance; tool

DESCRIPTION (provided by applicant): One of the most devastating birth defects affect the neural crest, a highly migratory stem cell-like population that contribute to craniofacial and cardiovascular development, and peripheral and enteric nervous system assembly. Cell lineage tracing and tissue transplantation studies have revealed the neural crest cell (NCC) migratory pathways emerge as discrete segregated streams, separated by neural-crest-free exclusion zones that appear to prevent the intermixing of NCC subpopulations and ensure their arrival at precise targets. These findings support the premise that neural crest cell guidance cues derive from the embryonic microenvironment and cell communication. Most noteworthy are the data we have generated in vivo showing cell-cell and cell-environment interactions may influence the directional migration of the neural crest. Based on these observations, we propose to test the central hypothesis that the microenvironment and cell-cell interactions associated with the neural crest-rich regions of the embryo contain informational cues with the potential to direct cells to precise targets. Our long term goal is to understand the biological mechanisms underlying neural crest migration that ultimately results in organ development. Our short term goal is to identify the key cellular and molecular mechanisms underlying the sculpting of cranial NCC migratory streams within an in vivo model. Using in vivo molecular perturbations and embryo microsurgery, together with photoactivation cell labeling, 4-D confocal imaging, cell tracking and cell behavior analyses, we propose to: Aim 1: Characterize the specific and dynamic cellular interactions essential for cranial neural crest migration using in vivo photoactivation cell labeling, 4-D confocal imaging, cell tracking and cell behavior analyses. Aim 2: To determine the role of neuropilins within the embryonic microenvironment in signaling and modulating neural crest migration. Aim 3: Investigate the role of the embryonic microenvironment in signaling and modulating neural crest migration, with particular focus on neuropilin- semaphorin and neuropilin-VEGF interactions. Public Health Relevance: At the completion of these studies, we expect to have an increased understanding of guidance cues and pathways that directly modulate neural crest migration that could be translated for novel therapeutic applications.

描述（由申请人提供）：最具破坏性的先天缺陷会影响神经rest，这是一种高度迁移的干细胞样人群，有助于颅面和心血管发育，以及周围和肠神经系统组装。细胞谱系追踪和组织移植研究已经揭示了神经rest细胞（NCC）迁移途径作为离散的隔离流出现，被无神经克雷斯特的无神经排除区分开，这些区域似乎可以防止NCC的相互混合，并确保其确切的目标到达。这些发现支持这样的前提：神经rest细胞引导提示源自胚胎微环境和细胞通信。最值得注意的是我们在体内产生的数据显示细胞 - 环境和环境相互作用可能会影响神经rest的定向迁移。基于这些观察结果，我们建议检验中心假设，即与胚胎的神经富富区域相关的微环境和细胞 - 细胞相互作用包含有可能将细胞引导到精确靶标的信息提示。我们的长期目标是了解最终导致器官发育的神经rest迁移的生物学机制。我们的短期目标是确定体内模型中颅内NCC迁移流雕刻的关键细胞和分子机制。我们使用光激活细胞标记，4-D共焦成像，细胞跟踪和细胞行为分析，使用光激活细胞标记，我们建议：AIM 1：表征特定和动态的细胞相互作用，表征颅神经cr迁移的特定和动态细胞相互作用，使用Vopopophopophopopophopopophopopopophopopopopophosactivativation Cylivativation Cell satrance antry contration和4-D-D-D-D-D Conforting，以及4-D-D-D-D-D-D-D-D-D-D-D-D Confrocal Imageing antry Imageing，我们建议使用体内分子扰动和胚胎显微外科手术。目标2：确定神经蛋白在胚胎微环境中的作用在信号传导和调节神经rest迁移中的作用。 AIM 3：研究胚胎微环境在信号传导和调节神经rest迁移中的作用，特别关注神经蛋白 - 词素和神经蛋白-VEGF的相互作用。 公共卫生相关性：完成这些研究后，我们希望对指导线索和途径有更多的了解，这些线索和途径直接调节神经rest迁移，该迁移可以用于新的治疗应用。