Transcriptional pathways regulating organ development in the mammalian embryo A major goal of our laboratory is to define the transcriptional pathways regulating tissue specific specification and differentiation during embryonic development. Current work in the lab is focused on the pathways controlling the development of cardiac, skeletal, and smooth muscle. We are also investigating the early events regulating the development of the liver, neural crest, and vascular endothelium. Members of the myocyte enhancer factor 2 (MEF2) family of transcription factors play key roles in the differentiation of a wide variety of embryonic lineages. One of our major goals is to define the early upstream genetic pathways regulating the development of many of those lineages where MEF2 factors are expressed. Therefore, to begin to dissect these early developmental pathways, we are defining the transcriptional regulation of the mef2c gene in transgenic mice. Mef2c is controlled by multiple separate, modular enhancers that each govern expression in a single lineage where mef2c is expressed. Molecular dissection of each of these separate enhancers has provided us with multiple new insights into mammalian development and has helped us to better understand the pathways controlling the switch from specification to differentiation. Another major goal of the lab is to define the embryological origins of cells that ultimately contribute to the cardiovascular system. We know that the myocardium itself is derived from at least two distinct sources in the embryo and that cells from the neural crest and septum transversum also contribute to cells within the developing heart. We are using a combination of conditional gene knockouts and fate mapping techniques in mice to gain greater insight into the embryological origins of the heart, outflow tract, vascular system, epicardium, and liver. We are especially interested in the development of the cardiac outflow tract and right ventricle from the anterior/secondary heart field.