Abstract 3406: A Novel Endothelin Receptor Type A-Expressing Cell Lineage Contributing to the Mouse Heart Development
In cardiovascular development, endothelin-1 (ET-1), acts on cardiac neural crest cells through endothelin type-A receptor (EdnrA) and is involved in the normal formation of pharyngeal artery-derived great vessels and ventricular septum. In addition, the formation of myocardial layer and conduction system is also reported to require the ET signals. To identify target cells of the ET-1/EdnrA signaling in heart development, we knocked-in the lacZ and EGFP genes into the mouse EdnrA locus by the Cre recombinase-mediated cassette exchange system. In developing heart, lacZ was expressed in cardiac neural crest-derived structures in the outflow tract and pharyngeal arteries. In addition, lacZ expression was also detected along the ventral ridge of the cardiac crescent at 3-somite stage. Subsequently, lacZ expression was confined to the inflow region around the sinus venosus and then extended to the left lateral aspect of the inflow tract. This expression did not overlap with expression of secondary heart field markers (Fgf10, Isl1), but was included in the Nkx2.5-positive primary heart field. This suggests that lacZ-positive cells might be a distinct cell subpopulation in the primary heart field, especially localized in the ventral inflow region. When we injected PKH67 into presumptive lacZ- or EGFP-positive region around the sinus venosus at E8.25, PKH-labeled cells were distributed to the region demarked by lacZ or EGFP expression after 24 h. Moreover, the lacZ expression patterns coincided with HCN4, a sinoatrial node marker, during E8.0 to E10.5; thereafter lacZ- and HCN4-expressing cells became mostly segregated. These findings suggest that EdnrA-lacZ-positive cells in the inflow tract may represent an as-yet-undefined cell lineage in heart development and may play an important role in asymmetric chamber formation and conduction system development.