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

(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

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
foxa1	aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg}	standard conditions	Long-pec	gut	ISH	Fig. 1 S2
foxa1	aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg}	standard conditions	Long-pec	liver	ISH	Fig. 1 S2
foxa1	aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg}	standard conditions	Long-pec	pancreatic bud	ISH	Fig. 1 S2
foxa1	WT	standard conditions	Long-pec	gut	ISH	Fig. 1 S2
foxa1	WT	standard conditions	Long-pec	liver	ISH	Fig. 1 S2
foxa1	WT	standard conditions	Long-pec	pancreatic bud	ISH	Fig. 1 S2
foxa2	aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg}	standard conditions	Long-pec	pharyngeal epithelium	ISH	Fig. 1 S2
foxa2	WT	standard conditions	Long-pec	pharyngeal epithelium	ISH	Fig. 1 S2
foxa3	aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg}	standard conditions	Long-pec	gut	ISH	Fig. 1 S2
foxa3	aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg}	standard conditions	Long-pec	liver	ISH	Fig. 1 S2

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: SB 431542	Long-pec	eye fused with eye, abnormal	Fig. 2
WT	chemical treatment: SB 505124	50%-epiboly	margin mespaa expression absent, abnormal	Fig. 4
WT + MO1-tdgf1	standard conditions	30%-epiboly	nodal signaling pathway decreased occurrence, abnormal	Fig. 2
WT + MO1-tdgf1	standard conditions	Prim-5	larval heart development decreased process quality, abnormal	Fig. 3
WT + MO1-tdgf1 + MO2-aplnrb + MO7-aplnra	standard conditions	Prim-5	cardiac muscle cell myl7 expression absent, abnormal	Fig. 3
WT + MO1-tdgf1 + MO2-aplnrb + MO7-aplnra	standard conditions	Prim-5	eye fused with eye, abnormal	Fig. 3
WT + MO1-tdgf1 + MO2-aplnrb + MO7-aplnra	standard conditions	Prim-5	larval heart development decreased process quality, abnormal	Fig. 3
WT + MO2-aplnrb + MO7-aplnra	standard conditions	50%-epiboly	margin mespaa expression decreased amount, abnormal	Fig. 4
WT + MO2-aplnrb + MO7-aplnra	standard conditions	50%-epiboly	margin mespab expression decreased amount, abnormal	Fig. 4
WT + MO2-aplnrb + MO7-aplnra	standard conditions	30%-epiboly	nodal signaling pathway decreased occurrence, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hu4145		Point Mutation	aplnrb
imb1		Small Deletion	aplnra
s608		Point Mutation	aplnrb
twu34Tg	Tg(myl7:EGFP)	Transgenic Insertion
zm00177433Tg	Tg(ZM)	Transgenic Insertion	aplnra

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
aplnra	MO7-aplnra	MRPHLNO
aplnra	TALEN2-aplnra	TALEN
aplnrb	MO2-aplnrb	MRPHLNO
lft1	MO3-lft1	MRPHLNO
tdgf1	MO1-tdgf1	MRPHLNO

Fish

Fish
aplnra^imb1/imb1
aplnra^{zm00177433Tg/zm00177433Tg}
aplnrb^{hu4145/hu4145}
aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg}
aplnrb^{hu4145/hu4145}; aplnra^{zm00177433Tg/zm00177433Tg} + MO3-lft1
aplnrb^{hu4145/hu4145} + MO3-lft1
aplnrb^s608/s608
aplnrb^s608/s608 + MO3-lft1
WT
WT + MO1-tdgf1

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Deshwar et al., 2016 ZDB-PUB-160415-6 PMID:27077952

The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development

Deshwar et al., 2016

ZDB-PUB-160415-6
PMID:27077952