CORE--FUNCTIONAL ANALYSIS /EXPRESSION

唇腭裂是一种主要的出生缺陷，通常被用作人类胚胎发生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，并且受到特定的充分研究的例子的影响。将个体基因的位点和阶段特异性表达模式整合到模式生物发育面部的全面代表中，是解剖这些途径的关键的第一步。功能分析/表达核心将这种方法与功能“敲低”分析的最新进展相结合，以协助项目在临床重要的形态发生事件中检查非冗余基因功能的证据。这一核心将利用创新技术提供资源

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.