Titre : | Role of the MYOD/NFATC2 complex into myofiber formation and specification during mouse myogenesis : Acte de colloque : 4ème colloque international de Myologie (9-13 mai 2011; Lille (France)) |
contenu dans : | |
Auteurs : | Daou N ; Saclier M ; Baghdadi M ; Lécolle S ; della Gaspera B ; Charbonnier F ; Chanoine C ; Kjaer M ; Chazaud B |
Type de document : | Article |
Editeur : | AFM-TELETHON, 2011 |
Pages : | p 171 |
Langues: | Anglais |
Résumé : |
Poster
Calcineurin/NFAT (Nuclear Factor of Activated T-cells) signaling is involved in multiple aspects of skeletal muscle development and disease. A number of studies demonstrate that calcineurin plays a regulatory role in skeletal muscle adaptation and muscle regeneration by its ability to promote myotube differentiation. Calcineurin dephosphorylates members of NFAT transcription factors allowing NFAT translocation into the nucleus where it cooperates with other transcription factors to induce transcription of target genes. Recently, we demonstrated that calcineurin/NFATc3 signaling is required for primary myogenesis by transcriptional cooperation with the basic helix loop helix transcription factor MyoD (Armand et al. 2008) which is crucial in somite differentiation.Here, we show that the NFATc2 isoform is also able to physically interact with MyoD. However, NFATc2 and MyoD interaction is unique, since the interacting domains are different from those involved in the NFATc3/MyoD interaction. The biological significance of such NFATc2/MyoD interaction is completely unknown and is likely crucial as myod:nfatc2 double deletion is lethal. Our ongoing data demonstrate that myod:nfatc2 double mutant embryos display three distinct muscle phenotypes, suggesting a synergistic cooperation between MyoD and NFATc2 in several cellular events. Atrophy was observed in E18.5 double mutant embryos but to the same extent as in nfatc2 null embryos, showing the involvement of NFATc2 in the control of myofiber size. In contrast, muscles from nfatc2:myod mutant embryos were characterized by a marked decrease of the number of myofibers in comparison to wild-type and simple mutant embryos, demonstrating for the first time a cooperative effect of NFATc2 and MyoD in acquiring the correct number of muscle fibers during embryogenesis. Furthermore, the muscle typology of double mutant embryos was modified. In vivo, the MyoD/NFATc2 complex is crucial for neonatal myosin heavy chain (MHC) expression since the proportion of myofibers expressing this isoform is dramatically decreased in myod:nfatc2 double mutants.Altogether these data show that NFATc2 and MyoD cooperate in vivo during late myogenesis. This NFATc2/MyoD interaction likely represents a key to better understand the genetic and cellular basis of myofiber formation and specification during myogenesis. |