ZFIN ID: ZDB-PUB-090921-29
A novel functional role of iduronate-2-sulfatase in zebrafish early development
Moro, E., Tomanin, R., Friso, A., Modena, N., Tiso, N., Scarpa, M., and Argenton, F.
Date: 2010
Source: Matrix biology : journal of the International Society for Matrix Biology   29(1): 43-50 (Journal)
Registered Authors: Argenton, Francesco, Modena, Nicola, Moro, Enrico, Tiso, Natascia
Keywords: iduronate sulfatase, zebrafish, development
MeSH Terms:
  • Animals
  • Body Patterning/physiology*
  • Craniofacial Abnormalities/genetics
  • Craniofacial Abnormalities/pathology
  • Craniofacial Abnormalities/physiopathology
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/enzymology*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Humans
  • Iduronate Sulfatase/genetics
  • Iduronate Sulfatase/metabolism*
  • Molecular Sequence Data
  • Mucopolysaccharidosis II/genetics
  • Mucopolysaccharidosis II/pathology
  • Mucopolysaccharidosis II/physiopathology
  • Oligonucleotides, Antisense/genetics
  • Oligonucleotides, Antisense/metabolism
  • SOX Transcription Factors/genetics
  • SOX Transcription Factors/metabolism
  • Signal Transduction/physiology
  • Zebrafish/anatomy & histology
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 19761845 Full text @ Matrix Biol.
Sulfated glycosaminoglycan chains of extracellular matrix and cell membrane-tethered proteoglycans exert specific cellular functions by interacting with a broad spectrum of morphogens and growth factors. In humans, a congenital impaired catabolism of sulfated glycosaminoglycans is associated with severe metabolic disorders. Here, we report on the identification and characterization of a zebrafish iduronate sulfatase orthologue. By knocking down its function with antisense morpholino oligos, we demonstrate that iduronate sulfatase plays a critical role during early vertebrate development and its downregulation may be responsible for severe developmental defects, including a misshapen trunk and abnormal craniofacial cartilages. We show that the altered cartilage patterning is mediated by depauperation of sox10-expressing neural crest cell precursors. Through the application of a transactivation reporter assay, we also provide a molecular proof that increased TGF(R) (Transforming Growth Factor (R)) signalling is tightly associated with downregulation of iduronate sulfatase function. Our results provide insight into the early biological impairments underlying the Hunter syndrome and suggest the use of zebrafish as a novel tool to better understand lysosomal storage disorders pathogenesis.