PUBLICATION

Clec14a genetically interacts with Etv2 and Vegf signaling during vasculogenesis and angiogenesis in zebrafish

Authors

Pociute, K., Schumacher, J.A., Sumanas, S.

ID

ZDB-PUB-190407-5

Date

2019

Source

BMC Developmental Biology 19: 6 (Journal)

Registered Authors

Schumacher, Jennifer, Sumanas, Saulius

Keywords

Angiogenesis, Clec14, Etsrp, Vascular endothelial, Vasculogenesis, Vegf, Zebrafish, etv2

MeSH Terms

Animals
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Zebrafish/embryology*
Zebrafish/genetics
Gene Expression Regulation, Developmental/genetics*
Neovascularization, Physiologic/genetics
Neovascularization, Physiologic/physiology*
Cell Differentiation/genetics
Vascular Endothelial Growth Factor A/genetics
Vascular Endothelial Growth Factor A/metabolism*
Signal Transduction/genetics
Animals, Genetically Modified
Gene Knockout Techniques

(all 14)

PubMed

30953479 Full text @ BMC Dev. Biol.

Abstract

Background C-lectin family 14 Member A (Clec14a) is a transmembrane protein specifically expressed in vascular endothelial cells during embryogenesis. Previous in vitro and in vivo studies have provided conflicting data regarding Clec14a role in promoting or inhibiting angiogenesis, therefore its functional role in vascular development remains poorly understood.

Results Here we have generated a novel clec14a mutant allele in zebrafish embryos using TALEN genome editing. clec14a mutant embryos exhibit partial defects and delay in the sprouting of intersegmental vessels. These defects in angiogenesis are greatly increased upon the knockdown of a structurally related C1qr protein. Furthermore, a partial knockdown of an ETS transcription factor Etv2 results in a synergistic effect with the clec14a mutation and inhibits expression of early vascular markers in endothelial progenitor cells, arguing that clec14a is involved in promoting vasculogenesis. In addition, Clec14a genetically interacts with Vegfa signaling. A partial knockdown of Vegfaa function in the clec14a mutant background resulted in a synergistic inhibition of intersegmental vessel sprouting.

Conclusions These results argue that clec14a is involved in both vasculogenesis and angiogenesis, and suggest that Clec14a genetically interacts with Etv2 and Vegf signaling during vascular development in zebrafish embryos.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-vegfaa	standard conditions	Prim-5	axial vasculature kdrl expression spatial pattern, abnormal	Fig. 5
WT + MO2-etsrp	standard conditions	14-19 somites	embryonic blood vessel endothelial progenitor cell cdh5 expression decreased amount, abnormal	Fig. 4
WT + MO2-etsrp	standard conditions	14-19 somites	embryonic blood vessel endothelial progenitor cell kdrl expression decreased amount, abnormal	Fig. 4
clec14a^ci15/ci15	standard conditions	14-19 somites	embryonic blood vessel endothelial progenitor cell cdh5 expression decreased amount, abnormal	Fig. 4
clec14a^ci15/ci15	standard conditions	14-19 somites	embryonic blood vessel endothelial progenitor cell kdrl expression decreased amount, abnormal	Fig. 4
clec14a^ci15/ci15	standard conditions	26+ somites	intermediate cell mass of mesoderm clec14a expression decreased amount, abnormal	Fig. 1
clec14a^ci15/ci15	standard conditions	Prim-5	axial vasculature kdrl expression spatial pattern, abnormal	Fig. 5
clec14a^ci15/ci15 + MO1-cd93	standard conditions	Prim-5	intersegmental vessel cdh5 expression decreased amount, abnormal	Fig. 3
clec14a^ci15/ci15 + MO1-cd93	standard conditions	Prim-5	intersegmental vessel cdh5 expression spatial pattern, abnormal	Fig. 3
clec14a^ci15/ci15 + MO1-cd93	standard conditions	Prim-5	intersegmental vessel cldn5b expression decreased amount, abnormal	Fig. 3

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ci15		Small Deletion	clec14a
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
cd93	MO1-cd93	MRPHLNO
clec14a	TALEN1-clec14a	TALEN
etsrp	MO2-etsrp	MRPHLNO
vegfaa	MO1-vegfaa	MRPHLNO

Fish

Fish
clec14a^ci15/ci15
clec14a^ci15/ci15 + MO1-cd93
clec14a^ci15/ci15 + MO1-vegfaa
clec14a^ci15/ci15 + MO2-etsrp
clec14a^ci15/ci15; s843Tg
clec14a^ci15/ci15; s843Tg + MO1-cd93
clec14a^ci15/ci15; s843Tg + MO1-vegfaa
clec14a^ci15/ci15; s843Tg + MO2-etsrp
s843Tg + MO1-cd93
s843Tg + MO1-vegfaa

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Pociute et al., 2019 ZDB-PUB-190407-5 PMID:30953479

Clec14a genetically interacts with Etv2 and Vegf signaling during vasculogenesis and angiogenesis in zebrafish

Pociute et al., 2019

ZDB-PUB-190407-5
PMID:30953479