UC San Diego

Vertebrate heart formation requires input from two temporally distinct phases of cardiomyocyte differentiation. Progenitors from the first heart field form the primitive heart tube in the initial phase. Then, in a subsequent phase, progenitors from the second heart field contribute additional cells to both poles of the heart. Recruitment of second heart field progenitor cells to the arterial pole creates the cardiac outflow tract (OFT), but the precise mechanisms responsible for controlling OFT progenitor production remain to be elucidated. Members of the Cadm family of cell adhesion molecules participate in both homophilic and heterophilic binding to regulate intercellular interactions and signaling. Previously, our laboratory had demonstrated that morpholino knockdown of cadm4 results in a dramatic OFT expansion, which is preceded by an increase in OFT progenitors. In order to extend our studies of Cadm4 function and to analyze its potential interactions with other Cadm family members, we have generated mutant alleles of cadm4, cadm2a, and cadm3 and analyzed their effects on OFT formation. Evaluation of OFT morphology and the OFT progenitor population in cadm4 mutants did not reveal significant defects in OFT development, in contrast with the cadm4 morphant phenotype. Similarly, we found that OFT formation was normal in cadm2a mutants, cadm3 mutants, cadm4;cadm2a double mutants, and cadm4;cadm3 double mutants. Altogether, our findings document a discrepancy between the phenotypes of cadm4 mutants and cadm4 morphants and lay the groundwork for future studies on whether and how Cadm molecules regulate OFT formation.