The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development
Open Access
- 14 April 2016
- journal article
- Published by eLife Sciences Publications, Ltd in eLife
- Vol. 5, e13758
- https://doi.org/10.7554/elife.13758
Abstract
The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development | 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.Funding Information
- Canadian Institutes of Health Research (Operating Grant 86663)
- Agency for Science, Technology and Research (Strategic Positioning Fund on Genetic Orphan Diseases)
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