PUBLICATION

Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development

Authors

Mitchell, I.C., Brown, T.S., Terada, L.S., Amatruda, J.F., and Nwariaku, F.E.

ID

ZDB-PUB-100126-18

Date

2010

Source

PLoS One 5(1): e8807 (Journal)

Registered Authors

Amatruda, James F.

Keywords

none

MeSH Terms

Animals
Animals, Genetically Modified
Antigens, CD/genetics
Antigens, CD/metabolism*
Base Sequence
Blood Vessels/embryology*
Blood Vessels/metabolism
Cadherins/genetics
Cadherins/metabolism*
DNA Primers
Gene Knockdown Techniques
In Situ Hybridization
Zebrafish/embryology*

(all 13)

PubMed

20098718 Full text @ PLoS One

Abstract

BACKGROUND: Vascular endothelial cadherin (VE-cad) is essential for endothelial barrier integrity and vascular sprouting. However, the role of this important protein in cardiovascular development is only recently becoming apparent. METHODOLOGY/PRINCIPAL FINDINGS: To characterize the role of VE-cadherin in cardiovascular development, we analyzed cardiovascular development in a zebrafish VE-cad knockdown model. Embryos deficient in VE-cad show profoundly impaired cardiac development despite having apparently normal peripheral vasculature. Initial formation of the heart proceeds normally in knockdown embryos, but subsequent looping morphogenesis is impaired. Consistent with these results, VE-cad knockdown embryos demonstrate impaired cardiac function and early circulatory arrest. Histologic examination of knockdown embryos shows persistent, abnormal separation of the endocardial and myocardial layers. Using transmission electron microscopy, we demonstrate that endocardial junctions form poorly in VE-cad knockdown embryos, with resulting leak across the endothelial layer and reduction in the density of the cardiac jelly. CONCLUSIONS: Our results demonstrate a significant role for VE-cadherin in cardiac development independent of its effects on the formation of the peripheral vasculature.

Genes / Markers

Marker	Marker Type	Name
cdh5	GENE	cadherin 5
myh7	GENE	myosin heavy chain 7
myl7	GENE	myosin, light chain 7, regulatory

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
myh7	AB	control	Protruding-mouth	cardiac ventricle	ISH	Fig. 4
myh7	AB + MO5-cdh5	standard conditions	Protruding-mouth	cardiac ventricle	ISH	Fig. 4
myl7	AB	control	Day 4	heart	ISH	Fig. 4
myl7	AB	control	Protruding-mouth	heart	ISH	Fig. 4
myl7	AB + MO5-cdh5	standard conditions	Day 4	heart	ISH	Fig. 4
myl7	AB + MO5-cdh5	standard conditions	Protruding-mouth	heart	ISH	Fig. 4

1 - 6 of 6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO1-cdh5	standard conditions	Prim-15 to Day 4	blood circulation disrupted, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Long-pec	blood circulation disrupted, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Long-pec	heart looping disrupted, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Long-pec	pericardium edematous, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Long-pec to Day 4	heart looping disrupted, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Long-pec to Day 4	pericardium edematous, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Protruding-mouth	blood circulation disrupted, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Protruding-mouth	heart looping disrupted, abnormal	Fig. 2
AB + MO1-cdh5	standard conditions	Protruding-mouth	pericardium edematous, abnormal	Fig. 2
AB + MO5-cdh5	standard conditions	Prim-15 to Day 4	blood circulation disrupted, abnormal	Fig. 2

1 - 10 of 42

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
y1Tg	Tg(fli1:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Mitchell et al., 2010 ZDB-PUB-100126-18 PMID:20098718

Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development

Mitchell et al., 2010

ZDB-PUB-100126-18
PMID:20098718