Conditional mutagenesis of Rac1 or Cdc42 in mice significantly impaired myoblast fusion, reducing the fusion index from 52% in controls to 8% and 26%, respectively.
Rac1 and Cdc42 are essential for myoblast fusion in mice, functioning in a nonredundant manner to recruit vinculin and cytoskeletal proteins to contact sites.
Absolute Event Rate: 8% vs 52%
Rac1 and Cdc42 are small G-proteins that regulate actin dynamics and affect plasma membrane protrusion and vesicle traffic. We used conditional mutagenesis in mice to demonstrate that Rac1 and Cdc42 are essential for myoblast fusion in vivo and in vitro. The deficit in fusion of Rac1 or Cdc42 mutant myoblasts correlates with a deficit in the recruitment of actin fibers and vinculin to myoblast contact sites. Comparison of the changes observed in mutant myogenic cells indicates that Rac1 and Cdc42 function in a nonredundant and not completely overlapping manner during the fusion process. Our genetic analysis demonstrates thus that the function of Rac in myoblast fusion is evolutionarily conserved from insects to mammals and that Cdc42, a molecule hitherto not implicated in myoblast fusion, is essential for the fusion of murine myoblasts.
Vasyutina et al. (2009) studied Muscle development. Conditional mutagenesis of Rac1 and Cdc42 vs. Control mice (Rac1flox/+; Lbx1cre or Cdc42flox/+; Lbx1cre) was evaluated on Fusion index (percentage of myogenic nuclei present in multinucleated cells) at E14.5. Conditional mutagenesis of Rac1 or Cdc42 in mice significantly impaired myoblast fusion, reducing the fusion index from 52% in controls to 8% and 26%, respectively.