PUBLICATION
The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development
- Authors
- Deshwar, A.R., Chng, S.C., Ho, L., Reversade, B., Scott, I.C.
- ID
- ZDB-PUB-160415-6
- Date
- 2016
- Source
- eLIFE 5: (Journal)
- Registered Authors
- Chng, Serene, Deshwar, Ashish, Ho, Lena, REVERSADE, Bruno, Scott, Ian
- Keywords
- Aplnr, Cardiac progenitors, Heart development, Mesendoderm, Nodal, Zebrafish
- Datasets
- GEO:GSE58683
- MeSH Terms
-
- Animals
- Heart/embryology*
- Nodal Protein/metabolism*
- Receptors, G-Protein-Coupled/metabolism*
- Signal Transduction*
- Transforming Growth Factor beta/metabolism*
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 27077952 Full text @ Elife
Citation
Deshwar, A.R., Chng, S.C., Ho, L., Reversade, B., Scott, I.C. (2016) The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development. eLIFE. 5.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping