This is a competing renewal of a Program Project Grant, currently in its 16th year, which focuses on the? molecular regulation of lung development. The program has been highly successful in bringing together an? interactive multidisciplinary team of investigators to explore this theme, and has resulted in significant? contributions to the field. This renewal consists of four interactive projects to study determinants of cell fate? and differentiation in the developing lung. These projects address critical and poorly understood issues on? the mechanisms of establishment of lung cell lineages, and on how this relates to morphogenesis and? acquisition of differentiated cellular phenotypes.? Project 1 addresses questions related to how the initial respiratory lineages are spatially organized and? expanded during early morphogenesis, and the role of Notch and Fgfs in this process. Project 2 will focus on? the mechanisms by which endogenous microRNAs control dynamic gene activity during proximal-distal? specification of the lung. Project 3 develops new tools exploring a mouse ES cell culture system to study the? genetic mechanisms that control early lung lineage specification. Project 4 focuses on mechanisms of? chromatin remodeling and DMA methylation in the regulation of gene transcription during early lung? development.? Besides these projects, three cores are proposed. The """"""""Administrative Core"""""""" will deal with the overall? management and financial aspects of the Program. The """"""""Microscopy-Image Analysis and FACS Core"""""""" will? provide resources for histology, analysis of gene/protein expression by standard or confocal microscopy and? for cell sorting. The """"""""Mouse Core"""""""" will support the investigators in maintaining the various existing mouse? lines, breeding, genotyping, and for designing constructs of new mouse lines.? The projects and cores are designed to be highly interactive, with extensive sharing of expertise, reagents? and model systems. Results from these studies will provide relevant insights into mechanisms of lung? development and stem cell biology
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