CORE--FUNCTIONAL ANALYSIS /EXPRESSION

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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.