Organogenesis is a highly dynamic process involving orchestrated cell movements and multiple interactions of cells with their surrounding environment. The phenotype of a cell is defined by the genes that the cell expresses and this is controlled, in large part, at the level of transcription. Therefore, in order to understand the molecular mechanisms underlying differentiation and development of a given tissue or organ it is crucial to analyze the role of transcription factors in these processes. Most organs are comprised of multiple tissues and many different cell types and so it is difficult to determine the contribution of a given transcription factor to development of a specific organ. However, because 90 percent of the liver consists of a single cell type, the hepatocyte, the liver offers a relatively simple system in which to study the role of transcription factors in differentiation and organogenesis in vivo. The gene pescadillo has recently been identified by an insertional mutagenesis screen in zebrafish and has been found to be essential for fish liver development. An understanding of the transcriptional regulation of the murine homologue of pescadillo is, therefore, likely to contribute toward an understanding of the molecular mechanisms underlying early stages of mammalian hepatic development. Here we propose to isolate murine pescadillo cDNA and genomic clones and use them to i) investigate the tissue specific expression pattern of pescadillo during development in the mouse, and ii) begin a preliminary analysis of the transcriptional regulatory elements governing pescadillo's expression in the murine liver diverticulum. Overall, this proposal will provide a greater understanding of how hepatic cell fate decisions are directed during a critical phase of liver development. It will also significantly broaden our insight into liver growth and regeneration which is of utmost importance given the biomedical relevance of the liver.
