PUBLICATION

The receptor protein-tyrosine phosphatase, Dep1, acts in arterial/venous cell fate decisions in zebrafish development

Authors

Rodriguez, F., Vacaru, A., Overvoorde, J., and den Hertog, J.

ID

ZDB-PUB-081008-14

Date

2008

Source

Developmental Biology 324(1): 122-130 (Journal)

Registered Authors

den Hertog, Jeroen, Overvoorde, John, Rodriguez, Fiona

Keywords

Dep1, protein-tyrosine phosphatase, arterial, venous, cell specification, zebrafish, morpholino

MeSH Terms

Arteries/cytology
Arteries/embryology*
Endothelium, Vascular/cytology
Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism*
Receptors, Notch/metabolism
Cell Differentiation/physiology
Endothelial Cells/cytology*
Endothelial Cells/metabolism
Veins/cytology
Veins/embryology*
Signal Transduction/physiology
Zebrafish Proteins/metabolism
Animals
Embryo, Nonmammalian/physiology
Basic Helix-Loop-Helix Transcription Factors/metabolism
Zebrafish/embryology*
Zebrafish/metabolism
Phosphatidylinositol 3-Kinases/metabolism

(all 18)

PubMed

18835554 Full text @ Dev. Biol.

Abstract

Dep1 is a transmembrane protein-tyrosine phosphatase (PTP) that is expressed in vascular endothelial cells and has tumor suppressor activity. Mouse models with gene targeted Dep1 either show vascular defects, or do not show any defects at all. We used the zebrafish to investigate the role of Dep1 in early development. The zebrafish genome encodes two highly homologous Dep1 genes, Dep1a and Dep1b. Morpholinos specific for Dep1a and Dep1b induced defects in vasculature, resulting in defective blood circulation. However, Green Fluorescent Protein expression in fli1a::gfp1 transgenic embryos and cdh5 expression, markers of vascular endothelial cells, were normal upon Dep1a- and Dep1b-MO injection. Molecular markers indicated that arterial specification was reduced and venous markers were expanded in Dep1 morphants. Moreover, the Dep1a/Dep1b knockdowns were rescued by inhibition of Phosphatidylinositol-3 kinase (PI3K) and by expression of active Notch and Grl/Hey2. Our results suggest a model in which Dep1 acts upstream in a signaling pathway inhibiting PI3K, resulting in expression of Notch and Grl, thus regulating arterial specification in development.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
cdh5	AB/TL	standard conditions	Prim-15	axial vasculature	ISH	Fig. 6
cdh5	AB/TL	standard conditions	Prim-15	blood vessel endothelial cell	ISH	Fig. 6
cdh5	AB/TL + MO1-ptprja + MO1-ptprjb.1	standard conditions	Prim-15	axial vasculature	ISH	Fig. 6
cdh5	AB/TL + MO1-ptprja + MO1-ptprjb.1	standard conditions	Prim-15	blood vessel endothelial cell	ISH	Fig. 6
dab2	AB/TL	standard conditions	Prim-15	posterior cardinal vein	ISH	Fig. 7
dab2	AB/TL + MO1-ptprja + MO1-ptprjb.1	standard conditions	Prim-15	posterior cardinal vein	ISH	Fig. 7
efnb2a	AB/TL	standard conditions	Prim-15	dorsal aorta	ISH	Fig. 7
efnb2a	AB/TL + MO1-ptprja + MO1-ptprjb.1	standard conditions	Prim-15	dorsal aorta	ISH	Fig. 7
EGFP	y1Tg	standard conditions	Prim-15	blood vessel endothelial cell	IFL	Fig. 3
EGFP	y1Tg	standard conditions	Prim-15	dorsal aorta	IFL	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB/TL + MO1-ptprja	standard conditions	Prim-15	artery morphogenesis disrupted, abnormal	Fig. 6
AB/TL + MO1-ptprja	standard conditions	Prim-15	dorsal aorta morphology, abnormal	Fig. 4
AB/TL + MO1-ptprja	standard conditions	Prim-15	dorsal aorta morphology, abnormal	Fig. 6
AB/TL + MO1-ptprja	standard conditions	Long-pec	axial vasculature decreased functionality, abnormal	Fig. 3
AB/TL + MO1-ptprja	standard conditions	Long-pec	blood circulation disrupted, abnormal	Fig. 3
AB/TL + MO1-ptprja	standard conditions	Long-pec	blood decreased fluid flow, abnormal	Fig. 3
AB/TL + MO1-ptprja	standard conditions	Long-pec	dorsal aorta increased accumulation blood, abnormal	Fig. 3
AB/TL + MO1-ptprja	standard conditions	Long-pec	posterior cardinal vein increased accumulation blood, abnormal	Fig. 3
AB/TL + MO1-ptprja	standard conditions	Prim-15	dorsal aorta morphology, abnormal	Fig. 5
AB/TL + MO1-ptprja + MO1-ptprjb.1	standard conditions	Prim-15	artery morphogenesis disrupted, abnormal	Fig. 6

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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
ptprja	MO1-ptprja	MRPHLNO
ptprja	MO2-ptprja	MRPHLNO
ptprjb.1	MO1-ptprjb.1	MRPHLNO

Fish

Fish
AB/TL
AB/TL + MO1-ptprja
AB/TL + MO1-ptprja + MO1-ptprjb.1
AB/TL + MO1-ptprjb.1
AB/TL + MO2-ptprja
y1Tg
y1Tg + MO1-ptprja
y1Tg + MO2-ptprja

Antibodies

Orthology

Gene	Orthology
ptprja
ptprjb.1

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Rodriguez et al., 2008 ZDB-PUB-081008-14 PMID:18835554

The receptor protein-tyrosine phosphatase, Dep1, acts in arterial/venous cell fate decisions in zebrafish development

Rodriguez et al., 2008

ZDB-PUB-081008-14
PMID:18835554