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| Item Type: | Preprint |
|---|---|
| Title: | c-MAF transduces motor neuron firing to sustain fast-glycolytic myofibers and neuromuscular junctions |
| Creators Name: | Jauliac, Edgar, Backer, Stephanie, Sadaki, Shunya, Gondin, Julien, Fessard, Aurelie, Escoffier, Hugues, Roullat, Maeva, Di Gallo, Maxime, Levesque, Adrien, Pereira, Doriane, Dos Santos, Mattieu, Vuong, Vincent, Ham, Alexander, Letourneur, Franck, Pierre, Remi, Rüegg, Markus A., Birchmeier, Carmen, Fujita, Ryo, Sotiropoulos, Athanassia and Maire, Pascal |
| Abstract: | This study investigates how motoneuron firing influences transcription factor binding site enrichment in mouse fast glycolytic Myh4+ adult myofibers. Using single nucleus multi-omic analysis of innervated versus denervated tibialis anterior (TA) muscles, we identified a shift in transcription factor binding sites on active chromatin: SIX and c-MAF binding sites were enriched in Myh4+ myonuclei of innervated fibers but are replaced by JUN, FOS, and RUNX1 sites upon denervation. These findings suggest that c-MAF activity functions downstream of fast motoneuron firing. Supporting this, c-MAF shows robust nuclear enrichment in muscles stimulated at 100 Hz and during periods of increased motoneuron firing when mice are active, but is absent in denervated muscles. Thus, c-MAF bZIP transcription factor act as primary readouts of fast motoneuron firing in skeletal muscles. To clarify c-MAF’s regulatory network, constitutive and inducible skeletal muscle-specific c-Maf mutants were analyzed. Loss of cMAF resulted in atrophy of MYH4+ myofibers in specific distal hindlimb muscles, mirroring phenotypes seen in ALS and sciatic denervation models, while other muscles remained unaffected. Further, c-MAF was found to regulate neuromuscular junction (NMJ) stability. Following c-Maf deletion, NMJs became progressively fragmented, accompanied by increased motoneuron terminal sprouting and ectopic reinnervation of myofibers as demonstrated by kinetics following c-Maf deletion. Overall, this work establishes c-MAF as a critical mediator linking motoneuron firing to muscle gene regulation, fiber integrity, and NMJ maintenance in fast glycolytic fibers of specific muscles. |
| Keywords: | Animals, Mice |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2026.02.05.703983 |
| Date: | 8 February 2026 |
| Official Publication: | https://doi.org/10.64898/2026.02.05.703983 |
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