Complex transcriptional factor cascades regulating lung development remain poorly understood. Studies in both lower organism model systems and vertebrates indicate that GATA family zinc-finger transcription factors are key regulators of endoderm development. GATA6 is the only known member of the GATA family expressed in the forming bronchial epithelium as it buds from the foregut endoderm and GATA6 knockout cells fail to integrate into the bronchial epithelium in chimeric embryos. GATA6 binding sites are present in the promoters of numerous genes integral to organ-specific function of the lung. Thus, GATA6 is likely an important developmental regulator of lung-specific differentiation. The goals of this proposal are to: 1) define the spatial and temporal pattern of GATA6 gene and protein expression in the lung; 2) examine protein-protein interactions that modulate transcriptional activity of GATA6 in the lung; 3) determine the function of GATA6 in bronchial epithelial cells and the developing mouse lung using a """"""""dominant-repressor"""""""" approach. These studies may provide important new information regarding GATA6 transcriptional factor regulation of lung development and organ-specific differentiation.
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