PUBLICATION

Hedgehog signaling via angiopoietin1 is required for developmental vascular stability

Authors

Lamont, R.E., Vu, W., Carter, A.D., Serluca, F.C., MacRae, C.A., and Childs, S.J.

ID

ZDB-PUB-100223-30

Date

2010

Source

Mechanisms of Development 127(3-4): 159-168 (Journal)

Registered Authors

Childs, Sarah J., Lamont, Ryan, MacRae, Calum A., Serluca, Fabrizio

Keywords

Iguana, Hemorrhage, Zebrafish, Angiopoietin, Hedgehog

MeSH Terms

Hedgehog Proteins/metabolism*
Zebrafish/embryology*
Signal Transduction*
In Situ Hybridization
Microscopy, Electron
Microscopy, Confocal
Blood Vessels/embryology*
Animals
Angiopoietin-1/physiology*

(all 9)

PubMed

20156556 Full text @ Mech. Dev.

Abstract

The molecular pathways by which newly formed, immature endothelial cell tubes remodel to form a mature network of vessels supported by perivascular mural cells are not well understood. The zebrafish iguana (igu) genetic mutant has a mutation in the daz-interacting protein 1 (dzip1), a member of the hedgehog signaling pathway. Loss of dzip1 results in decreased size of the cranial dorsal aortae, ultrastructural defects in perivascular mural cell recruitment and subsequent hemorrhage. Although hedgehog signaling is disrupted in igu mutants, we find no defects in vessel patterning or artery-vein specification. Rather, we show that the loss of angiopoietin1 (angpt1) expression in ventral perivascular mesenchyme is responsible for vascular instability in igu mutants. Over-expression of angpt1 or partial down-regulation of the endogenous Angpt1 antagonist angpt2 rescues hemorrhage. This is the first direct in vivo link between hedgehog signaling and the induction of vascular stability by recruitment of perivascular mural cells through angiopoietin signaling.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
angpt1	dzip1^fo10a/fo10a	standard conditions	Prim-5		heart tube	ISH	Fig. 4
angpt1	dzip1^fo10a/fo10a	standard conditions	Prim-5		hypochord	ISH	Fig. 4
angpt1	dzip1^fo10a/fo10a	standard conditions	Prim-5	Not Detected	ventral mesenchyme	ISH	Fig. 4
angpt1	smo^nv122/nv122	standard conditions	Prim-5		ventral mesenchyme	ISH	Fig. S7
angpt1	WT	standard conditions	Prim-5		heart tube	ISH	Fig. 4
angpt1	WT	standard conditions	Prim-5		hypochord	ISH	Fig. 4
angpt1	WT	standard conditions	Prim-5		ventral mesenchyme	ISH	Fig. 4
angpt1	WT	standard conditions	Prim-5		ventral mesenchyme	ISH	Fig. S7
angpt2b	dzip1^fo10a/fo10a	standard conditions	Prim-5		vascular endothelium	ISH	Fig. 4
angpt2b	WT	standard conditions	Prim-5		vascular endothelium	ISH	Fig. 4

1 - 10 of 20

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-angpt1	standard conditions	Long-pec	blood circulation arrested, abnormal	Fig. 4
WT + MO1-angpt1	standard conditions	Long-pec	heart edematous, abnormal	Fig. 4
WT + MO1-angpt1	standard conditions	Long-pec	heart morphogenesis process quality, abnormal	Fig. 4
WT + MO1-angpt2b	standard conditions	Long-pec	blood circulation arrested, abnormal	Fig. 4
WT + MO1-angpt2b	standard conditions	Long-pec	heart edematous, abnormal	Fig. 4
WT + MO1-angpt2b	standard conditions	Long-pec	heart morphogenesis process quality, abnormal	Fig. 4
dzip1^fo10a/+; dzip1^tm79a/+	standard conditions	Long-pec	blood vessel development process quality, abnormal	Fig. 1
dzip1^fo10a/+; dzip1^tm79a/+	standard conditions	Long-pec	cranial vasculature hemorrhagic, abnormal	Fig. 1
dzip1^fo10a/fo10a	standard conditions	Prim-5	ventral mesenchyme physical object quality, abnormal	Fig. 4
dzip1^fo10a/fo10a	standard conditions	Long-pec	blood vessel development process quality, abnormal	Fig. 1

1 - 10 of 21

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fo10a		Point Mutation	dzip1
la116Tg	Tg(kdrl:GFP)	Transgenic Insertion
nv122		Point Mutation	smo
tm79a		Point Mutation	dzip1
y7Tg	Tg(fli1:nEGFP)	Transgenic Insertion

1 - 5 of 5

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
angpt1	MO1-angpt1	MRPHLNO
angpt1	MO2-angpt1	MRPHLNO
angpt2b	MO1-angpt2b	MRPHLNO
angpt2b	MO2-angpt2b	MRPHLNO

Fish

Fish
dzip1^fo10a/fo10a
dzip1^fo10a/fo10a; y7Tg
dzip1^fo10a/+; dzip1^tm79a/+
dzip1^tm79a/tm79a
la116Tg
smo^nv122/nv122
WT
WT + MO1-angpt1
WT + MO1-angpt2b
y7Tg

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Entity Type	Entity Symbol	Location
Feature	fo10a	Chr: 6 Details
GENE	dzip1	Chr: 6 Details
SSLP	z11310	Chr: 6 Details
SSLP	z17212	Chr: 6 Details

Lamont et al., 2010 ZDB-PUB-100223-30 PMID:20156556

Hedgehog signaling via angiopoietin1 is required for developmental vascular stability

Lamont et al., 2010

ZDB-PUB-100223-30
PMID:20156556