Somatic muscle formation is an unusual process as it requires the cells involved, the myoblasts, to relinquish their individual state and fuse with one another to form a syncitial muscle fiber. The potential use of myoblast fusion therapies to rebuild damaged muscles has generated continuing interest in elucidating the molecular basis of the fusion process. Yet, until recently, few of the molecular players involved in this process had been identified. Now, however, it has been possible to couple a detailed understanding of the cellular basis of the fusion process with powerful classical and molecular genetic strategies in the Drosophila embryo. We review the cellular studies, and the recent genetic and biochemical analyses that uncovered interacting extracellular molecules present on fusing myoblasts and the intracellular effectors that facilitate fusion. With the conservation of proteins and protein functions across species, it is likely that these findings in Drosophila will benefit understanding of the myoblast fusion process in higher organisms.

Sidestep (Side) is a pivotal molecular player in embryonic motor axon pathfinding. But questions about its functional repertoire remain: (i) can Side permanently overturn targeting preferences? (ii) does it promote synaptogenesis, and (iii) can Side facilitate synaptic stabilization? To address these questions, Side was temporally and spatially misexpressed and the visible consequences for neuromuscular junction morphology were assessed. When Side was misexpressed either broadly or selectively in muscles during targeting in a wildtype background motor axon targeting preferences were permanently overturned. However the misexpression of Side in all muscles post-targeting neither changed synapse morphology, nor compensated for a lack of the synapse-stabilizing protein Fasciclin II (FasII). Rather Side appears to be dependent on FasII, instead of on intrinsic ability, for sustaining targeting changes. We propose that Side helps to bring motor axons to their correct muscle targets and promotes synaptogenesis, then FasII serves to stabilize the synaptic contacts.

Hibris encodes a protein that is a newly identified member of the immunoglobulin superfamily and has homology to vertebrate Nephrins and Drosophila Sticks-and-Stones. The Hibris protein has eight Ig-like domains, a fibronectin domain and a 160 amino acid cytoplasmic tail. The hibris transcript is expressed in a broad range of tissues and across life stages. In the embryo, hibris transcript is present in the mesectoderm, then in a group of cells at the developing CNS midline and in a subset of glia. In the periphery, hibris is expressed by fusion competent myoblasts and the epidermal muscle attachment site cells. Deletion analyses show that loss of hibris does not visibly affect embryonic CNS or somatic muscle development. However overexpressing hibris in the somatic mesoderm disrupts myoblast fusion. Furthermore, when overexpressed in the epidermis, Hibris causes comprehensive derangement of muscle insertion locations. A similar myoblast fusion defect is observed when the Drosophila homologs of DM-GRASP/BEN/SC1 (irregular chiasm-roughest and dumbfounded) are deleted together. Our S2 cell aggregation assays have revealed a heterotypic interaction between Hibris and Dumbfounded, but not between Hibris and Irregular Chiasm-Roughest. We propose that Hibris is an extracellular partner for Dumbfounded and potentially mediates the response of myoblasts to this attractant.