Neural Crest Genes in Craniofacial Development

描述(申请人提供)：整个头面部骨骼起源于颅神经脊，这是一种在中枢神经系统形成的迁移细胞类型，可以广泛迁移并分化为面部的软骨和骨骼。本研究的目的是为了更好地了解颅面神经发育的分子调控，鉴定和鉴定在脑神经脊区表达的基因。我的初步结果描述了迁移前神经脊细胞的基因表达谱，并确定了参与颅面图案形成的候选调控分子。在该奖项的第一阶段，将详细分析其中两个在发育中的脑神经脊强表达的基因的功能，并将进行筛选，以确定在神经脊迁移过程中表达的新基因。我们将使用体内和体外的方法，在鸡胚胎和携带神经粘连蛋白-2零突变的小鼠身上，分析神经粘连蛋白-2受体及其配体在脑神经脊区的作用。伴随的是，一个与神经脊前体高度特异的同源性未知的基因，将通过功能获得和功能丧失技术在鸡颅神经脊中进行功能表征。在脑神经脊移行过程中表达的基因将在基因组规模的阵列屏幕上进行识别。在该奖项的第二阶段，将通过传统方法(鸡的过度抑制和小鼠突变体的创建)来分析其他基因的功能，此外，还将提议构建神经脊特异阵列，用于探测不同条件下脑神经脊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大学的Marianne Bronner-Fraser博士的实验室进行，Marianne Bronner-Fraser博士是美国最受尊敬的研究型大学之一的神经脊研究领域的领导者。候选人劳拉·甘米尔博士自1999年以来一直是布朗纳-弗雷泽博士实验室的博士后学者。到目前为止，这位候选人的努力一直是创造一种独特的大阵列试剂，用于识别与早期神经脊发育有关的大量基因集合。目前的职业目标是发展鸡和老鼠胚胎学领域的研究专长，并练习指导技能，以获得学术教职。长期的职业目标是经营一个实验室，进行神经脊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.