Midline fusion of the bilateral heart primordial is an early and essential morphogenetic step during the formation of a functional heart tube. Without this fusion, the two cardiac primordia develop in isolated contralateral positions, resulting in an embryonic malformation known as cardia bifida--or split heart. The long-term goal of the research project outlined in this proposal is to understand how the Nodal signaling pathway controls heart differentiation, migration, and L/R asymmetry. Specifically, phenotypic, genetic, and molecular characterization of a recently isolated mutation that affects zebrafish heart formation will be performed. Preliminary phenotypic analysis suggests that this is a new locus in the Nodal signaling pathway. Morphology and molecular probes will be used to perform a thorough phenotypic and gene expression analysis in order to determine what relevant developmental processes are perturbed. This new locus will also be mapped and cloned, allowing further genetic and molecular characterization of the gene, as well as placement of the gene into a genetic pathway leading to heart differentiation and early migration.
