The SCAR and WASp nucleation-promoting factors act sequentially to mediate Drosophila myoblast fusion.

The actin nucleation-promoting factors SCAR/WAVE and WASp, together with associated elements, mediate the formation of muscle fibres through myoblast fusion during Drosophila embryogenesis. Our phenotypic analysis, following the disruption of these two pathways, suggests that they function in a sequential manner. Suppressor of cyclic AMP receptor (SCAR) activity is required before the formation of pores in the membranes of fusing cells, whereas Wiskott-Aldrich syndrome protein (WASp) promotes the expansion of nascent pores and completion of the fusion process. Genetic epistasis experiments are consistent with this step-wise temporal progression. Our observations further imply a separate, Rac-dependent role for the SCAR complex in promoting myoblast migration. In keeping with the sequential utilization of the two systems, we observe abnormal accumulations of filamentous actin at the fusion sites when both pathways are disrupted, resembling those present when only SCAR-complex function is impaired. This observation further suggests that actin-filament accumulation at the fusion sites might not depend on Arp2/3 activity altogether.