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

Zebrafish Proteins/metabolism*
Receptors, G-Protein-Coupled/metabolism*
Nodal Protein/metabolism*
Heart/embryology*
Transforming Growth Factor beta/metabolism*
Signal Transduction*
Zebrafish
Animals

(all 8)

PubMed

27077952 Full text @ Elife

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

Figures