A central function for perlecan in skeletal muscle and cardiovascular development

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.

DOI: 10.1083/jcb.200708022

Extracted Key Phrases

8 Figures and Tables

050100200920102011201220132014201520162017
Citations per Year

268 Citations

Semantic Scholar estimates that this publication has 268 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Zoeller2008ACF, title={A central function for perlecan in skeletal muscle and cardiovascular development}, author={Jason J. Zoeller and Angela McQuillan and John M Whitelock and Shiu-Ying Ho and Renato V. Iozzo}, journal={The Journal of Cell Biology}, year={2008}, volume={181}, pages={381 - 394} }