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SIX1 and SIX4 homeoproteins regulate PAX7+ progenitor cell properties during fetal epaxial myogenesis

Item Type:Article
Title:SIX1 and SIX4 homeoproteins regulate PAX7+ progenitor cell properties during fetal epaxial myogenesis
Creators Name:Wurmser, M. and Chaverot, N. and Madani, R. and Sakai, H. and Negroni, E. and Demignon, J. and Saint-Pierre, B. and Mouly, V. and Amthor, H. and Tapscott, S. and Birchmeier, C. and Tajbakhsh, S. and Le Grand, F. and Sotiropoulos, A. and Maire, P.
Abstract:Pax7 expression marks stem cells in developing skeletal muscles and adult satellite cells during homeostasis and muscle regeneration. The genetic determinants that control the entrance into the myogenic program and the appearance of PAX7+ cells during embryogenesis are poorly understood. SIX homeoproteins are encoded by the Sine oculis homeobox related Six1-Six6 genes in vertebrates. Six1, Six2, Six4 and Six5 are expressed in the muscle lineage. Here we tested the hypothesis that Six1 and Six4 could participate in the genesis of myogenic stem cells. We show that fewer PAX7+ cells occupy a satellite cell position between the myofiber and its associated basal lamina in Six1 and Six4 (s1s4KO) at E18. However, PAX7+ cells are detected in remaining muscle masses present in the epaxial region of the double mutant embryos and are able to divide and contribute to muscle growth. To further characterize the properties of s1s4KO PAX7+ cells, we analyzed their transcriptome and tested their properties after transplantation in adult regenerating tibialis anterior (TA) muscle. Mutant stem cells form hypotrophic myofibers that are not innervated but retain the ability to self-renew.
Keywords:Homeodomain Proteins, Knockout Mice, Muscle Development, Skeletal Muscle, PAX7 Transcription Factor, Stem Cells, Trans-Activators, Animals, Mice
Publisher:Company of Biologists
Page Range:dev185975
Date:9 October 2020
Official Publication:https://doi.org/10.1242/dev.185975
PubMed:View item in PubMed

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