Neural Crest Genes in Craniofacial Development

描述（由申请人提供）：整个颅面骨骼起源于颅神经嵴，颅神经嵴是一种在中枢神经系统中形成的迁移细胞类型，广泛迁移并分化为面部的软骨和骨。这项建议的目的是确定和功能特性的基因表达的颅神经嵴，以更好地了解颅面发育的分子调控。我的初步结果描述了一个迁移前神经嵴细胞的基因表达谱，并确定了参与颅面图案的候选调控分子。在该奖项的第一阶段，将详细分析其中两个在颅神经嵴发育中强烈表达的基因的功能，并进行筛选以确定神经嵴迁移过程中表达的新基因。神经纤毛蛋白-2受体及其配体在颅神经嵴中的作用将在鸡胚胎和神经纤毛蛋白-2无效突变小鼠中使用体内和体外方法进行分析。伴随性，一个基因，没有已知的同源性，是高度特异性的神经嵴前体将在鸡颅神经嵴功能的获得和功能丧失的技术。在颅神经嵴迁移过程中表达的基因将在基因组规模的阵列筛选中鉴定。在该奖项的第二阶段，其他基因的功能将通过传统的方法（鸡的超表达和小鼠突变体的创建）进行分析，除了建议的神经嵴特异性阵列的构建，可用于探测在不同条件下颅神经嵴发育过程中的基因表达。该奖项的学者发展阶段将在加州理工学院的Marianne Bronner-Fraser博士的实验室进行，该实验室是该国最受推崇的研究型大学之一的神经嵴研究领域的领导者。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，候选人的努力一直是创造一种独特的宏阵列试剂，用于识别参与早期神经嵴发育的大量基因。近期的职业目标是发展鸡和小鼠胚胎学领域的研究专业知识，并实践指导技能，以获得学术教师职位。长期的职业目标是经营一个实验室，从事神经嵴和颅面发育的基础研究。

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.