PUBLICATION

A central function for perlecan in skeletal muscle and cardiovascular development

Authors
Zoeller, J.J., McQuillan, A., Whitelock, J., Ho, S.Y., and Iozzo, R.V.
ID
ZDB-PUB-080429-1
Date
2008
Source
The Journal of cell biology   181(2): 381-394 (Journal)
Registered Authors
Ho, Shiu-Ying
Keywords
none
MeSH Terms
  • Animals
  • Blood Vessels/drug effects
  • Blood Vessels/embryology*
  • DNA Primers
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/physiology
  • Fetal Heart/drug effects
  • Fetal Heart/physiology*
  • Heparan Sulfate Proteoglycans/genetics*
  • Muscle, Skeletal/blood supply
  • Muscle, Skeletal/drug effects
  • Muscle, Skeletal/embryology*
  • Neovascularization, Physiologic/drug effects
  • Oligonucleotides, Antisense/pharmacology*
  • Zebrafish/embryology
PubMed
18426981 Full text @ J. Cell Biol.
Abstract
Perlecan's developmental functions are difficult to dissect in placental animals because perlecan disruption is embryonic lethal. In contrast to mammals, cardiovascular function is not essential for early zebrafish development because the embryos obtain adequate oxygen by diffusion. In this study, we use targeted protein depletion coupled with protein-based rescue experiments to investigate the involvement of perlecan and its C-terminal domain V/endorepellin in zebrafish development. The perlecan morphants show a severe myopathy characterized by abnormal actin filament orientation and disorganized sarcomeres, suggesting an involvement of perlecan in myopathies. In the perlecan morphants, primary intersegmental vessel sprouts, which develop through angiogenesis, fail to extend and show reduced protrusive activity. Live videomicroscopy confirms the abnormal swimming pattern caused by the myopathy and anomalous head and trunk vessel circulation. The phenotype is partially rescued by microinjection of human perlecan or endorepellin. These findings indicate that perlecan is essential for the integrity of somitic muscle and developmental angiogenesis and that endorepellin mediates most of these biological activities.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping