The ADAMTS5 Metzincin Regulates Zebrafish Somite Differentiation

The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish adamts5 during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of myod expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5. These data identify a non-enzymatic function for ADAMTS5 in regulating an important cell signaling pathway that impacts on muscle development, with implications for musculoskeletal diseases in which ADAMTS5 and Shh have been associated.

• Publication year

  2018

• Venue

  International Journal of Molecular Sciences

• Publication date

  2018-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/ijms19030766PMID 29518972PMCID 5877627
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2012cited by this paper
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  2012cited by this paper
• Duplication of 7q36.3 encompassing the Sonic Hedgehog (SHH) gene is associated with congenital muscular hypertrophy.

  2012cited by this paper
• The ADHD-susceptibility gene lphn3.1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development

  2012cited by this paper
• Wnt signaling in myogenesis.

  2012cited by this paper
• Altered versican cleavage in ADAMTS5 deficient mice; a novel etiology of myxomatous valve disease.

  2011cited by this paper
• Cooperation of two ADAMTS metalloproteases in closure of the mouse palate identifies a requirement for versican proteolysis in regulating palatal mesenchyme proliferation

  2010cited by this paper
• Hedgehog signaling and laminin play unique and synergistic roles in muscle development

  2010cited by this paper
• Modulating hedgehog signaling can attenuate the severity of osteoarthritis

  2009cited by this paper
• ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression.

  2009cited by this paper
• Characterization of proADAMTS5 processing by proprotein convertases.

  2009cited by this paper
• Muscle development is disrupted in zebrafish embryos deficient for fibronectin

  2008cited by this paper
• The Secreted Metalloprotease ADAMTS20 Is Required for Melanoblast Survival

  2008cited by this paper
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  2008cited by this paper
• Multimodal signaling by the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) promotes neurite extension.

  2008cited by this paper
• ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-β bioavailability regulation

  2008cited by this paper
• High-resolution in situ hybridization to whole-mount zebrafish embryos

  2007cited by this paper
• Essential and overlapping roles for laminin α chains in notochord and blood vessel formation

  2006cited by this paper
• Essential and overlapping roles for laminin alpha chains in notochord and blood vessel formation.

  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2005cited by this paper
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  2005cited by this paper
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  2005cited by this paper
• Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis

  2005cited by this paper
• Role of ADAMTS-1 in atherosclerosis: remodeling of carotid artery, immunohistochemistry, and proteolysis of versican.

  2004cited by this paper
• Zebrafish slow muscle cell migration induces a wave of fast muscle morphogenesis.

  2004cited by this paper
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  2004cited by this paper
• ADAMTS1: A Matrix Metalloprotease with Angioinhibitory Properties

  2003cited by this paper
• Force transmission via axial tendons in undulating fish: a dynamic analysis.

  2002cited by this paper
• Zebrafish mutants identify an essential role for laminins in notochord formation.

  2002cited by this paper
• Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function.

  2001cited by this paper
• The zebrafish neckless mutation reveals a requirement for raldh2 in mesodermal signals that pattern the hindbrain.

  2001cited by this paper
• Effective targeted gene ‘knockdown’ in zebrafish

  2000cited by this paper
• Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish.

  1998cited by this paper
• Sonic Hedgehog induces proliferation of committed skeletal muscle cells in the chick limb.

  1998cited by this paper
• Notochord induction of zebrafish slow muscle mediated by Sonic hedgehog.

  1997influential reference
• Identification of separate slow and fast muscle precursor cells in vivo, prior to somite formation.

  1996cited by this paper
• Stages of embryonic development of the zebrafish

  1995cited by this paper
• Ectopic expression of Sonic hedgehog alters dorsal-ventral patterning of somites.

  1994cited by this paper
• Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.

  1994cited by this paper
• Sonic hedgehog mediates the polarizing activity of the ZPA.

  1993cited by this paper
• Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation.

  1993cited by this paper
• Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

  1991cited by this paper
• Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation

  1991cited by this paper
• Smith ScholarWorks Smith ScholarWorks

  year unknowncited by this paper

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  2025cites this paper
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  2025cites this paper
• In dystrophic mdx hindlimb muscles where fibrosis is limited versican haploinsufficiency transiently improves contractile function without reducing inflammation.

  2024cites this paper
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  2020cites this paper
• Extracellular Matrix in Development and Disease

  2019cites this paper