Pax3/Pax7 Regulate Skeletal Muscle Formation: from Development to Postnatal Myogenesis
Abstract
Pax3 and Pax7 are key upstream transcription factors regulating progenitor and stem cells of several tissues. Over the last 15 years, the scientists have identified Pax3 and Pax7 regulated genes involved in control of the myogenic programme. However, the overall molecular mechanisms underlying function and tissue-specific activity of these factors remains elusive. The speaker and his research group undertook complementary approaches, combining genetically-modified mouse models, large-scale analysis, molecular and cellular approaches to analyse Pax3 and Pax7 function during development and postnatal myogenesis. They have performed large-scale analysis of Pax3 targets and identified several genes and pathways regulating skeletal muscle development. They used gene targeting to evaluate the conserved and diversified functions of Pax3 and Pax7 transcription factors via gene replacement. They have also examined the role of Pax3 isoforms function in vivo by replacing endogenous Pax3 with an embryonic-specific isoform, Pax3c, which is abundant at the early stages of development. While development is rescued in these animals, the speaker found a striking skeletal muscle impairment of regeneration following cardiotoxin-mediated injury, associated with loss of quiescence for the muscle stem cells. This result points to a specific function for Pax3 in postnatal skeletal muscle.
About the speaker
Prof Frédéric Relaix received his PhD in Molecular and Cellular Developmental Biology from Université Pierre et Marie Curie (UMPC) in 1998. He joined the Institut Pasteur as a Research Associate in 2000 and returned to UMPC in 2006 as the INSERM Research director of the Mouse Molecular Genetics group. In 2015, he moved to University Paris-Est Créteil and is currently the Professor of Medicine.
Prof Relaix’s research focuses on the molecular and cellular mechanisms of skeletal muscle progenitor and stem cells specification, maintenance, growth arrest and differentiation using mouse molecular genetics, as well as understanding the function of the Pax3 and Pax7 genes during development, evolution, skeletal muscle formation, neural crest cells, nervous system development and cancer.
Prof Relaix received the Scientific Prize from La Ligue des Yvelines in 2006. He was also a member of editorial board of the Skeletal Muscle Journal and NPJ Regenerative Medicine Journal.
