Project Summary The heart is composed of a broad range of diverse cardiac cell types, which organize into distinct cardiac structures that coordinately regulate cardiac function and circulation throughout the body. Despite efforts devoted toward understanding how these cardiac cell types are created in order to develop potential human cardiac therapies and/or illuminate underlying mechanisms/etiologies of congenital heart disease (CHD), our understanding of how diverse cardiac cell types emerge from developmental heart field progenitors, and how they organize into heart structures remains to be fully defined. Thus, we propose to identify and investigate the cardiovascular developmental regulators and gene regulatory networks that direct the development of Juxta- Cardiac Field (JCF)-derived cardiovascular cell types creating the mammalian heart. Toward this end, a multi- disciplinary experimental and computational systems biology approach will be employed to: (1) examine the contribution of JCF progenitors to the developing heart, (2) investigate how JCF progenitors differentiate into specific cell types contributing to heart development and (3) investigate whether mechanisms in JCF development are conserved in human heart development.