PUBLICATION

Endocardial identity is established during early somitogenesis by Bmp signalling acting upstream of npas4l and etv2

Authors

Capon, S.J., Uribe, V., Dominado, N., Ehrlich, O., Smith, K.A.

ID

ZDB-PUB-220510-18

Date

2022

Source

Development (Cambridge, England) 149(9): (Journal)

Registered Authors

Capon, Sam, Ehrlich, Ophelia, Smith, Kelly

Keywords

etv2/etsrp, npas4l/cloche, Bmp signalling, Cardiac, Endocardium, Zebrafish

Datasets

GEO:GSE201611

MeSH Terms

Endocardium*/metabolism
Zebrafish*/genetics
Zebrafish*/metabolism
Animals
Signal Transduction/genetics
Zebrafish Proteins/metabolism
Gene Expression Regulation, Developmental

(all 7)

PubMed

35531980 Full text @ Development

Abstract

The endocardium plays important roles in the development and function of the vertebrate heart; however, few molecular markers of this tissue have been identified and little is known about what regulates its differentiation. Here, we describe the Gt(SAGFF27C); Tg(4xUAS:egfp) line as a marker of endocardial development in zebrafish. Transcriptomic comparison between endocardium and pan-endothelium confirms molecular distinction between these populations and time-course analysis suggests differentiation as early as eight somites. To investigate what regulates endocardial identity, we employed npas4l, etv2 and scl loss-of-function models. Endocardial expression is lost in npas4l mutants, significantly reduced in etv2 mutants and only modestly affected upon scl loss-of-function. Bmp signalling was also examined: overactivation of Bmp signalling increased endocardial expression, whereas Bmp inhibition decreased expression. Finally, epistasis experiments showed that overactivation of Bmp signalling was incapable of restoring endocardial expression in etv2 mutants. By contrast, overexpression of either npas4l or etv2 was sufficient to rescue endocardial expression upon Bmp inhibition. Together, these results describe the differentiation of the endocardium, distinct from vasculature, and place npas4l and etv2 downstream of Bmp signalling in regulating its differentiation.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	Prim-5	endocardium	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	14-19 somites	endocardium	RNA-Seq	Fig. 2
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	20-25 somites	endocardium	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	5-9 somites	endocardium	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	1-4 somites	endocardium	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	Long-pec	endocardium	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	14-19 somites	endocardium	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	10-13 somites	endocardium	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	10-13 somites	olfactory placode	RNA-Seq	Fig. 3
cbfa2t3	map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	Prim-5	otic vesicle	RNA-Seq	Fig. 3

1 - 10 of 75

Show

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO4-tal1	standard conditions	14-19 somites	endocardium myl7 expression increased amount, abnormal	Fig. 4
WT + MO4-tal1	standard conditions	14-19 somites	endocardium myl7 expression spatial pattern, abnormal	Fig. 4
WT + MO4-tal1	standard conditions	14-19 somites	endocardium spi1b expression increased amount, abnormal	Fig. 4
WT + MO4-tal1	standard conditions	14-19 somites	endocardium spi1b expression spatial pattern, abnormal	Fig. 4
WT + MO4-tal1	standard conditions	14-19 somites	endocardium EGFP expression increased amount, abnormal	Fig. 4
WT + MO4-tal1	standard conditions	14-19 somites	endocardium EGFP expression spatial pattern, abnormal	Fig. 4
etsrp^{uq13ks/uq13ks}; map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	14-19 somites	endocardium myl7 expression spatial pattern, abnormal	Fig. 4
etsrp^{uq13ks/uq13ks}; map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	14-19 somites	endocardium spi1b expression decreased amount, abnormal	Fig. 4
etsrp^{uq13ks/uq13ks}; map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	14-19 somites	endocardium EGFP expression decreased amount, abnormal	Fig. 4
etsrp^{uq13ks/uq13ks}; map3k22^{nksagff27cGt/nksagff27cGt}	standard conditions	14-19 somites	endocardium EGFP expression decreased amount, abnormal	Fig. 7

1 - 10 of 34

Show

Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fr13Tg	Tg(hsp70l:bmp2b)	Transgenic Insertion
fr14Tg	Tg(hsp70l:nog3)	Transgenic Insertion
nksagff27cGt	Gt(GAL4FF)	Transgenic Insertion	map3k22
nkuasgfp1aTg	Tg(5xUAS:EGFP)	Transgenic Insertion
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion
s916Tg	Tg(kdrl:Hsa.HRAS-mCherry)	Transgenic Insertion
uq13ks		Small Deletion	etsrp
uq14ks		Small Deletion	npas4l
uq35ksTg	Tg(myl7:mCherry-CAAX)	Transgenic Insertion
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion

1 - 10 of 10

Show

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
gata1a	MO1-gata1a	MRPHLNO
spi1b	MO1-spi1b	MRPHLNO
tal1	MO4-tal1	MRPHLNO

Fish

Fish
etsrp^{uq13ks/uq13ks}
etsrp^{uq13ks/uq13ks}; map3k22^{nksagff27cGt/nksagff27cGt}
etsrp^{uq13ks/uq13ks}; map3k22^{nksagff27cGt/nksagff27cGt}; fr13Tg/fr13Tg
etsrp^{uq13ks/uq13ks}; map3k22^{nksagff27cGt/nksagff27cGt}; fr14Tg/fr14Tg
fr13Tg/fr13Tg
fr14Tg/fr14Tg
map3k22^{nksagff27cGt/nksagff27cGt}
map3k22^{nksagff27cGt/nksagff27cGt}; fr13Tg/fr13Tg
map3k22^{nksagff27cGt/nksagff27cGt}; fr14Tg/fr14Tg
map3k22^{nksagff27cGt/nksagff27cGt}; s916Tg/s916Tg

1 - 10 of 14

Show

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
GAL4FF	EFG	GAL4FF
mCherry	EFG	mCherry

Mapping

Capon et al., 2022 ZDB-PUB-220510-18 PMID:35531980

Endocardial identity is established during early somitogenesis by Bmp signalling acting upstream of npas4l and etv2

Capon et al., 2022

ZDB-PUB-220510-18
PMID:35531980