Neural Crest Genes in Craniofacial Development

颅面发育中的神经嵴基因

• 批准号: 7324450
• 负责人: LAURA S GAMMILL
• 金额: --
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7324450
• 关键词: biotechnology; cell migration; chick embryo; craniofacial; dental development; developmental genetics; developmental neurobiology; enzyme mechanism; gene expression; gene mutation; genetic screening; genetically modified animals; laboratory mouse; microarray technology; neural crest; neurogenetics

DESCRIPTION (provided by applicant): The entirety of the craniofacial skeleton arises from the cranial neural crest, a migratory cell type that forms in the central nervous system, migrates extensively and differentiates into the cartilage and bone of the face. The aim of this proposal is to identify and functionally characterize genes expressed in the cranial neural crest in order to better understand the molecular regulation of craniofacial development. My preliminary results have described a gene expression profile of a premigratory neural crest cell and have identified candidate regulatory molecules involved in craniofacial patterning. In the first phase of the award, the function of two of these genes that are strongly expressed in developing cranial neural crest will be analyzed in detail, and a screen will be carried out to identify new genes expressed during neural crest migration. The role of the receptor neuropilin-2 and its ligands in the cranial neural crest will be analyzed using in vivo and vitro approaches in chicken embryos and in mice bearing neuropilin-2 null mutations. Concomitanity, a gene with no known homology that is highly specific to neural crest precursors will be functionally characterized in chick cranial neural crest by gain-and loss of function techniques. Genes expressed during cranial neural crest migration will be identified in a genome-scale array screen. In the second phase of the award, the function of additional genes will be analyzed through traditional approaches (chick overpression and creation of the mouse mutants) in addition to the proposed construction of a neural crest-specific array that can be used to probe gene expression during cranial neural crest development under different conditions. The Scholar Development Phase of this award will be carried out in the lab of Dr. Marianne Bronner-Fraser at Caltech, a leader in the field of neural crest research at one of the most highly regarded research universities in the country. The candidate, Dr. Laura Gammill, has been a postdoctoral scholar in Dr. Bronner-Fraser's lab since 1999. The candidate's effort thus far has been to create a unique macroarray reagent that was used to identify a large collection of genes involved in early neural crest development. The immediate career goal is to develop research expertise in the area of chick and mouse embryology and to practice mentoring skills so as to obtain an academic faculty position. The long-term career goal is to run a laboratory doing basic research in neural crest and craniofacial development.

描述（由申请人提供）：全部颅面骨骼源自颅神经rest，颅神经rest是一种在中枢神经系统中形成的迁移细胞类型，广泛地迁移并区分了面部的软骨和骨骼。该提案的目的是识别并在功能上表征在颅神经rest中表达的基因，以便更好地了解颅面发育的分子调节。我的初步结果描述了前移民rest细胞的基因表达谱，并确定了参与颅面模式的候选调节分子。在该奖项的第一阶段，将详细分析这些基因中的两个基因的功能，这些基因将在开发颅神经rest中得到强烈表达，并将进行筛选以识别在神经rest迁移过程中表达的新基因。将使用体内和体外方法在鸡胚胎和带有Neuropilin-2 Null突变的小鼠中分析受体神经蛋白-2及其配体在颅神经crest中的作用。伴侣性是一种没有已知同源性的基因，该基因具有高度特异性的神经rest前体，将在鸡颅神经rest中通过功能技术的丧失和功能丧失在功能上表征。在颅神经rest迁移期间表达的基因将在基因组尺度阵列筛选中鉴定。在奖励的第二阶段中，除了在不同条件下在颅神经crest发育过程中，还可以使用传统的方法（小鸡的过度和创建小鼠突变体的鸡（小鼠的过度和创造））来分析其他基因的功能。该奖项的学者发展阶段将在加州理工学院的Marianne Bronner-Fraser博士的实验室中进行，该实验室是该国最受尊敬的研究所之一的神经rest研究领域的领导者。候选人Laura Gammill博士自1999年以来一直是Bronner-Fraser博士实验室的博士后学者。到目前为止，候选人的努力是创建一种独特的宏观阵列试剂，用于识别大量参与早期神经rest发育的基因。直接的职业目标是在小鸡和小鼠胚胎学领域发展研究专业知识，并练习指导技能，以获得学术职位。长期职业目标是运营一个实验室，从事神经rest和颅面发展的基础研究。