Perturbations in cell signaling elicit early cardiac defects in mucopolysaccharidosis type II

Roberto Costa, Andrea Urbani, Marika Salvalaio, Stefania Bellesso, Domenico Cieri, Ilaria Zancan, Mirella Filocamo, Paolo Bonaldo, Ildiko Szabò, Rosella Tomanin, Enrico Moro

Research output: Contribution to journalArticlepeer-review


Morphogens release and activity can be negatively affected by an impaired glycosaminoglycans (GAGs) turnover and proteoglycans assembly in the extracellular matrix, leading to altered tissue morphogenesis. In this work, we show that loss of Iduronate-2-sulfatase (IDS) activity, affecting GAGs catabolism and responsible for a life-threatening valvulopathy in mucopolysaccharidosis type II (MPSII), triggers early Sonic Hedgehog (Shh) and Wnt/β-catenin signaling defects, leading to aberrant heart development and atrioventricular valve formation in a zebrafish model. In addition, we consistently found impaired Shh signaling activity and cardiac electrophysiological abnormalities in IDS knockout mice at postnatal stages before any evident massive GAGs accumulation. These results suggest that IDS activity substantially affect cardiac morphogenesis through impaired Shh signaling and document an unexplored role of the enzyme in the fine-tuning of cell signaling pathways.

Original languageEnglish
Pages (from-to)1643-1655
Number of pages13
JournalHuman Molecular Genetics
Issue number9
Publication statusPublished - May 1 2017


  • Animals
  • Disease Models, Animal
  • Glycoproteins
  • Glycosaminoglycans
  • Hedgehog Proteins
  • Iduronate Sulfatase
  • Mice
  • Mice, Knockout
  • Mucopolysaccharidosis II
  • Myocardium
  • Proteoglycans
  • Wnt Signaling Pathway
  • Zebrafish
  • Zebrafish Proteins
  • beta Catenin
  • Journal Article
  • Research Support, Non-U.S. Gov't


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