CORE--FUNCTIONAL ANALYSIS /EXPRESSION

唇腭裂是一种主要的出生缺陷，通常用作人类胚胎发育复杂遗传疾病的模型。我们目前对驱动颅面发育的途径的协调和功能的理解是有限的，并且受到特定的研究实例的影响。将个体基因的位点特异性和阶段特异性表达模式整合到模式生物中发育面孔的综合表现中的能力是解剖这些途径的关键的第一步。功能分析/表达核心将结合联合收割机这一方法与功能“敲除”分析的最新进展，以协助项目检查临床重要形态发生事件期间非冗余基因功能的证据。这一核心将利用创新技术， P50的其他项目和核心，以加强基因发现的过程，并提高我们的 了解基因如何在复杂的途径中相互作用，在正常和异常的面部发育中发挥作用。核心将以一种直观的、可公开访问的方式呈现结果数据， 用于研究和教育目的。具体目标是： 1.将项目0003、0004、0005和Pilot产生的整装RNA原位杂交数据开发成小鼠胚胎颅面发育的四维图谱。 2.构建人类基因组区域（9 q）内所有基因的发育表达谱，并有强有力的证据表明与CL/P相关。 3.评估自组织图谱在从微阵列分析生成的转录谱预测候选基因中的应用 4.采用高通量基因敲除技术研究腭发育中特定候选基因的功能。

Cleft lip and palate is a major birth defect commonly used as a model for complex genetic diseases of human embryogenesis. Our current understanding of the coordination and function of the pathways driving craniofacial development is limited and biased by particular well-studied examples. The ability to integrate site- and stage- specific expression patterns of individual genes in a comprehensive representation of the developing face in model organisms is a critical first step towards dissection of these pathways. The functional analysis/expression core will combine this approach with the recent advances in functional 'knockdown" analysis to assist the projects in examining evidence of non-redundant gene-function during clinically important morphogenetic events. This core will use innovative technologies to provide resources to the other projects and cores of this P50 to enhance the process of gene discovery and improve our understanding of how genes interact in complex pathways that play a role in normal and abnormal facial development. The core will present the resulting data in an intuitive, publicly-accessible manner that can be used for both research and educational purposes. Specific aims will be to: 1. To develop whole-mount RNA in situ hybridization data generated by Projects 0003, 0004, 0005 and Pilot into a 4-dimensional atlas of craniofacial development in mouse embryos. 2. To construct developmental expression profiles for all genes within a human genomic region (9q) with strong evidence of linkage to CL/P. 3. To assess the use of self-organizing maps in predicting candidate genes from transcriptional profiles generated by microarray analysis 4. To determine the function of specific candidate genes in palate development using a high-throughput gene knockdown approach.