Abstract
The Apelin receptor (Apinr) is essential for heart development, controlling the early migration of cardiac progenitors. Here we demonstrate that in zebrafish Apinr modulates Nodal/TGF beta signaling, a key pathway essential for mesendoderm induction and migration. Loss of Apinr function leads to a reduction in Nodal target gene expression whereas activation of Apinr by a non-peptide agonist increases the expression of these same targets. Furthermore, loss of Apinr results in a delay in the expression of the cardiogenic transcription factors mespaa/ab. Elevating Nodal levels in apInra/b morphant and double mutant embryos is sufficient to rescue cardiac differentiation defects. We demonstrate that loss of Apinr attenuates the activity of a point source of Nodal ligands Squint and Cyclops in a non-cell autonomous manner. Our results favour a model in which Apinr is required to fine-tune Nodal output, acting as a specific rheostat for the Nodal/TGF beta pathway during the earliest stages of cardiogenesis.