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
- Oligonucleotides, Antisense/pharmacology*
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/physiology
- Neovascularization, Physiologic/drug effects
- DNA Primers
- Heparan Sulfate Proteoglycans/genetics*
- Blood Vessels/drug effects
- Blood Vessels/embryology*
- Zebrafish/embryology
- Muscle, Skeletal/blood supply
- Muscle, Skeletal/drug effects
- Muscle, Skeletal/embryology*
- Fetal Heart/drug effects
- Fetal Heart/physiology*
- PubMed
- 18426981 Full text @ J. Cell Biol.
Citation
Zoeller, J.J., McQuillan, A., Whitelock, J., Ho, S.Y., and Iozzo, R.V. (2008) A central function for perlecan in skeletal muscle and cardiovascular development. The Journal of cell biology. 181(2):381-394.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping