PUBLICATION

Ve-ptp Modulates Vascular Integrity by Promoting Adherens Junction Maturation

Authors

Carra, S., Foglia, E., Cermenati, S., Bresciani, E., Giampietro, C., Lora Lamia, C., Dejana, E., Beltrame, M., and Cotelli, F.

ID

ZDB-PUB-121221-13

Date

2012

Source

PLoS One 7(12): e51245 (Journal)

Registered Authors

Beltrame, Monica, Cotelli, Franco

Keywords

Embryos, Vascular permeability, Zebrafish, Tight junctions, Blood, Endothelial cells, Tails, Junctional complexes

MeSH Terms

Base Sequence
Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism*
DNA Primers
Adherens Junctions/enzymology
Adherens Junctions/physiology*
Animals
Reverse Transcriptase Polymerase Chain Reaction
Blotting, Western
In Situ Hybridization
Fluorescent Antibody Technique
Blood Vessels/enzymology
Blood Vessels/physiology*
Humans
Zebrafish
Neovascularization, Physiologic
Cells, Cultured

(all 16)

PubMed

23251467 Full text @ PLoS One

Abstract

Background

Endothelial cell junctions control blood vessel permeability. Altered permeability can be associated with vascular fragility that leads to vessel weakness and haemorrhage formation. In vivo studies on the function of genes involved in the maintenance of vascular integrity are essential to better understand the molecular basis of diseases linked to permeability defects. Ve-ptp (Vascular Endothelial-Protein Tyrosine Phosphatase) is a transmembrane protein present at endothelial adherens junctions (AJs).

Methodology/Principal Findings

We investigated the role of Ve-ptp in AJ maturation/stability and in the modulation of endothelial permeability using zebrafish (Danio rerio). Whole-mount in situ hybridizations revealed zve-ptp expression exclusively in the developing vascular system. Generation of altered zve-ptp transcripts, induced separately by two different splicing morpholinos, resulted in permeability defects closely linked to vascular wall fragility. The ultrastructural analysis revealed a statistically significant reduction of junction complexes and the presence of immature AJs in zve-ptp morphants but not in control embryos.

Conclusions/Significance

Here we show the first in vivo evidence of a potentially critical role played by Ve-ptp in AJ maturation, an important event for permeability modulation and for the development of a functional vascular system.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
ptprb	WT	standard conditions	Protruding-mouth	aortic arch	ISH	Fig. 2
ptprb	WT	standard conditions	Prim-5	aortic arch 1	ISH	Fig. 2
ptprb	WT	standard conditions	Prim-5	caudal vein plexus	ISH	Fig. 2
ptprb	WT	standard conditions	Long-pec	caudal vein plexus	ISH	Fig. 2
ptprb	WT	standard conditions	Protruding-mouth	cranial vasculature	ISH	Fig. 2
ptprb	WT	standard conditions	Long-pec	cranial vasculature	ISH	Fig. 2
ptprb	WT	standard conditions	Prim-5	cranial vasculature	ISH	Fig. 2
ptprb	WT	standard conditions	Prim-5	dorsal aorta	ISH	Fig. 2
ptprb	WT	standard conditions	Protruding-mouth	dorsal longitudinal anastomotic vessel	ISH	Fig. 2
ptprb	WT	standard conditions	Protruding-mouth	intersegmental vessel	ISH	Fig. 2

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO1-ptprb	standard conditions	Long-pec	blood vessel endothelial cell has fewer parts of type blood vessel endothelial cell cell-cell junction, abnormal	Fig. S5
AB + MO2-ptprb	standard conditions	Long-pec	adherens junction assembly disrupted, abnormal	Fig. 5
AB + MO2-ptprb	standard conditions	Long-pec	adherens junction assembly disrupted, abnormal	Fig. S5
AB + MO2-ptprb	standard conditions	Long-pec	blood circulation disrupted, abnormal	Fig. 3
AB + MO2-ptprb	standard conditions	Long-pec	blood vessel endothelial cell adherens junction immature, abnormal	Fig. 5
AB + MO2-ptprb	standard conditions	Long-pec	blood vessel endothelial cell adherens junction immature, abnormal	Fig. S5
AB + MO2-ptprb	standard conditions	Long-pec	blood vessel endothelial cell has fewer parts of type blood vessel endothelial cell cell-cell junction, abnormal	Fig. 5
AB + MO2-ptprb	standard conditions	Long-pec	blood vessel endothelial cell has fewer parts of type blood vessel endothelial cell cell-cell junction, abnormal	Fig. S5
AB + MO2-ptprb	standard conditions	Long-pec	caudal vein plexus broken, abnormal	Fig. 3
AB + MO2-ptprb	standard conditions	Long-pec	caudal vein plexus disorganized, abnormal	Fig. 3

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Mutations / Transgenics

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

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
ptprb	MO1-ptprb	MRPHLNO
ptprb	MO2-ptprb	MRPHLNO
ptprb	MO3-ptprb	MRPHLNO
tp53	MO4-tp53	MRPHLNO

Fish

Fish
AB + MO1-ptprb
AB + MO2-ptprb
AB + MO3-ptprb + MO4-tp53
WT
y1Tg
y1Tg + MO2-ptprb

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Carra et al., 2012 ZDB-PUB-121221-13 PMID:23251467

Ve-ptp Modulates Vascular Integrity by Promoting Adherens Junction Maturation

Background

Methodology/Principal Findings

Conclusions/Significance

Carra et al., 2012

ZDB-PUB-121221-13
PMID:23251467