Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle

Andrea Farini, Clementina Sitzia, Letizia Cassinelli, Federica Colleoni, Daniele Parolini, Umberto Giovanella, Simona Maciotta, Augusto Colombo, Mirella Meregalli, Yvan Torrente

Research output: Contribution to journalArticle

Abstract

Duchenne muscular dystrophy (DMD) is a progressiveneuromuscular disorder characterized by muscle wasting andpremature death. The defective gene is dystrophin, a structuralprotein, absence of which causes membrane fragility and myofibernecrosis. Several lines of evidence showed that in adult DMD patientsdystrophin is involved in signaling pathways that regulate calciumhomeostasis and differentiation programs. However, secondaryaspects of the disease, such as inflammation and fibrosisdevelopment, might represent a bias in the analysis. Because fetalmuscle is not influenced by gravity and does not suffer frommechanical load and/or inflammation, we investigated 12-week-oldfetal DMD skeletal muscles, highlighting for the first time earlyalterations in signaling pathways mediated by the absence ofdystrophin itself. We found that PLC/IP3/IPR3/Ryr1/Ca2+ signalingis widely active in fetal DMD skeletal muscles and, through thecalcium-dependent PKCα protein, exerts a fundamental regulatoryrole in delaying myogenesis and in myofiber commitment. These dataprovide new insights into the origin of DMD pathology during muscledevelopment.

Original languageEnglish
Pages (from-to)658-669
Number of pages12
JournalDevelopment
Volume143
Issue number4
DOIs
Publication statusPublished - Feb 15 2016

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Keywords

  • Calcium channels
  • DMD fetus
  • Dystrophin signaling
  • IP3/IP3R pathway
  • Myosin isoforms

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Farini, A., Sitzia, C., Cassinelli, L., Colleoni, F., Parolini, D., Giovanella, U., Maciotta, S., Colombo, A., Meregalli, M., & Torrente, Y. (2016). Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle. Development, 143(4), 658-669. https://doi.org/10.1242/dev.126193