TY - JOUR TI - The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development AU - Deshwar, Ashish R AU - Chng, Serene C AU - Ho, Lena AU - Reversade, Bruno AU - Scott, Ian C A2 - Robertson, Elizabeth VL - 5 PY - 2016 DA - 2016/04/14 SP - e13758 C1 - eLife 2016;5:e13758 DO - 10.7554/eLife.13758 UR - https://doi.org/10.7554/eLife.13758 AB - The Apelin receptor (Aplnr) is essential for heart development, controlling the early migration of cardiac progenitors. Here we demonstrate that in zebrafish Aplnr modulates Nodal/TGFβ signaling, a key pathway essential for mesendoderm induction and migration. Loss of Aplnr function leads to a reduction in Nodal target gene expression whereas activation of Aplnr by a non-peptide agonist increases the expression of these same targets. Furthermore, loss of Aplnr results in a delay in the expression of the cardiogenic transcription factors mespaa/ab. Elevating Nodal levels in aplnra/b morphant and double mutant embryos is sufficient to rescue cardiac differentiation defects. We demonstrate that loss of Aplnr 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 Aplnr is required to fine-tune Nodal output, acting as a specific rheostat for the Nodal/TGFβ pathway during the earliest stages of cardiogenesis. KW - Aplnr KW - Nodal KW - cardiac progenitors KW - heart development KW - mesendoderm JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -