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
-
- Angiopoietin-1/physiology*
- Animals
- Blood Vessels/embryology*
- Hedgehog Proteins/metabolism*
- In Situ Hybridization
- Microscopy, Confocal
- Microscopy, Electron
- Signal Transduction*
- Zebrafish/embryology*
- PubMed
- 20156556 Full text @ Mech. Dev.
Citation
Lamont, R.E., Vu, W., Carter, A.D., Serluca, F.C., MacRae, C.A., and Childs, S.J. (2010) Hedgehog signaling via angiopoietin1 is required for developmental vascular stability. Mechanisms of Development. 127(3-4):159-168.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping