Eya3 and Eya4 are two Eya genes expressed in adult myogenic stem cells, where they may act as SIX cofactors. We analyzed muscle regeneration in single and compound Eya3 and satellite cell-specific Eya4 mutant mice. A kinetic analysis of muscle regeneration after Notexin injury of the Tibialis Anterior revealed no major phenotype at 4, 14, and 30 days after injury in terms of PAX7+ cell number and myofiber cross-sectional area in Eya3 mutants, while all parameters were decreased in Eya4 mutants and further worsened in Eya3/Eya4 double mutants, in which we also observed a modification of the myofiber phenotype at 30 days after injury. Satellite cells were cultured ex vivo and Eya4 deletion was induced by Ad-Cre-mediated recombination. While single Eya3 mutant cells showed normal proliferation and differentiation, double mutant cells exhibited normal proliferation but failed to fuse. Analysis of their transcriptome revealed that the expression of Myomixer, Follistatin, and Noggin was severely downregulated specifically in double mutant cells, explaining their fusion deficiency. To gain a better understanding of the involvement of Eya genes during embryonic development and the genesis of PAX7+ myogenic stem cells, we analyzed Eya1-/-;Eya2-/-, Eya3-/-, Eya4-/-, and Eya3-/-;Eya4-/- E18.5 mutant fetuses at the limb and craniofacial levels. In Eya1-/-;Eya2-/- fetuses, we confirmed the absence of distal limb muscles and observed reduced craniofacial muscles. In Eya3-/-;Eya4-/- fetuses, craniofacial myogenesis appeared preserved and PAX7+ myogenic stem cells were present.
Viaut, C., Wurmser, M., Jauliac, E., Ben Driss, L., Backer, S., Madani, R., Issa, F., PIROZHKOVA, I., Sotiropoulos, A., Amthor, H., Maire, P.
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