ZFIN ID: ZDB-PUB-080429-1
A central function for perlecan in skeletal muscle and cardiovascular development
Zoeller, J.J., McQuillan, A., Whitelock, J., Ho, S.Y., and Iozzo, R.V.
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.
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.