title: 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.
authors.affiliation: Department of Pathology, Anatomy, and Cell, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Zoeller
authors.forename: Angela
authors.initials: A
authors.lastname: McQuillan
authors.forename: John
authors.initials: J
authors.lastname: Whitelock
authors.forename: Shiu-Ying
authors.initials: SY
authors.lastname: Ho
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000196:embryology*; D017931:DNA Primers; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology; D005318:Fetal Heart / Q000187:drug effects / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000196:embryology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D015027:Zebrafish / Q000196:embryology
chemical_list: D017931:DNA Primers; D019812:Heparan Sulfate Proteoglycans; D016376:Oligonucleotides, Antisense; C071927:perlecan