PUBLICATION

A unique role for 6-O sulfation modification in zebrafish vascular development

Authors
Chen, E., Stringer, S.E., Rusch, M.A., Selleck, S.B., and Ekker, S.C.
ID
ZDB-PUB-050714-10
Date
2005
Source
Developmental Biology   284(2): 364-376 (Journal)
Registered Authors
Ekker, Stephen C.
Keywords
Heparan sulfate 6-O sulfotransferase, Zebrafish, Vascular development, Morpholino
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Blood Vessels/embryology
  • Blood Vessels/growth & development*
  • Cloning, Molecular
  • Embryo, Nonmammalian
  • Embryonic Development
  • Expressed Sequence Tags
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins/metabolism
  • Heparitin Sulfate/metabolism
  • In Situ Hybridization
  • Microinjections
  • Molecular Sequence Data
  • Oligonucleotides, Antisense/pharmacology
  • Phylogeny
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Somites/metabolism
  • Sulfotransferases/antagonists & inhibitors
  • Sulfotransferases/chemistry
  • Sulfotransferases/genetics
  • Sulfotransferases/isolation & purification
  • Sulfotransferases/metabolism*
  • Zebrafish/embryology*
PubMed
16009360 Full text @ Dev. Biol.
Abstract
Heparan sulfate proteoglycans are important modulators of growth factor signaling in a variety of patterning processes. Secreted growth factors that play critical roles in angiogenesis bind to heparan sulfate, and this association is affected by 6-O-sulfation of the heparan sulfate chains. Addition of 6-O-sulfate is catalyzed by a family of sulfotransferases (HS6STs), and genetic manipulation of their function permits an assessment of their contribution to vascular assembly. We report on the biochemical activity and expression patterns of two zebrafish HS6ST genes. In situ hybridization reveals dynamic and distinct expression patterns of these two genes during development. Structural analysis of heparan sulfate from wild-type and morpholino antisense 'knockdown' embryos suggests that HS6ST-1 and HS6ST-2 have similar biochemical activity. HS6ST-2, but not HS6ST-1, morphants exhibit abnormalities in the branching morphogenesis of the caudal vein during embryonic development of the zebrafish. Our finding that HS6ST-2 is required for the branching morphogenesis of the caudal vein is the first in vivo evidence for an essential role of a gene encoding a heparan sulfate modifying enzyme in vertebrate angiogenesis. Our analysis of two zebrafish HS6ST genes suggests that a wide range of biological processes may be regulated by an array of sulfation-modifying enzymes in the vertebrate genome.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping