In Drosophila, the musculature consists of a stereotypic arrangement of distinct muscles and its development involves two types of myoblast: founder cells (FCs) and fusion-competent myoblasts (FCM). FCs, which are generated from progenitor cells selected from promuscular cell clusters,each fuse with several FCMs to form multinucleated myotubes that migrate under the ectoderm to their target tendons, with which they form strong attachments. This well-defined system is used to investigate many aspects of development,including, as reported in this issue, the control of cell identity, the mechanisms underlying cell fusion, and the control of cell migration and adherence.
On , Dubois and colleagues reveal how the Drosophila embryonic Dorsal/Acute 3(DA3) muscle lineage is specified. Sets of transcription factors are thought to endow each FC with the capacity to seed the formation of a distinct muscle type. To investigate this possibility, the researchers used the transcription factor Collier (Col), which is expressed in the DA3 muscle and is required for its formation, as a determinant and read-out of DA3 muscle identity. They discover that separate sets of cis-regulatory elements activate colin the DA3 promuscular cluster and in the FC progenitor cells and DA3 myofibre. In addition, they show that Col and Nautilus (which is also essential for DA3 muscle formation) act together to ensure that all the nuclei within the DA3 myofibre activate col and express the same differentiation program. Overall, these results support the concept of a combinatorial control of muscle identity.
On ,Richardson and co-workers use live imaging to shed new light on the involvement of cytoskeletal remodelling in myoblast fusion. They show that F-actin accumulates at sites of myoblast fusion and that these actin foci dissolve immediately before fusion occurs. Several mutations have been identified in Drosophila that disrupt myoblast fusion, including mutations in kette. Kette regulates SCAR/WAVE, an activator of Arp2/3-dependent actin polymerization. The researchers report that in kette mutant embryos, enlarged actin foci form that do not dissolve normally. Actin foci dissolution and myoblast fusion also fail in SCAR and Arp2/3 mutants. From their findings, the researchers suggest that Kette-SCAR-Arp2/3-mediated actin polymerization causes a reorganization of actin foci that is required for myoblast fusion and that actin dynamics may also be critical for other cell-cell fusion events.
Finally, on , Estrada and colleagues describe how the transmembrane cell adhesion protein Perdido (Perd), which is expressed in FCs and in growing myotubes, interacts with the Glutamate receptor interacting protein (Grip) and also with integrins to mediate myotube projection and attachment in Drosophila embryos. Both of these processes, the researchers report,are defective in perd loss-of-function mutants. In vitro, the Perd intracellular domain interacts with a PDZ domain in Grip, another muscle-expressed factor needed for myotube migration. Using a new,whole-embryo RNA interference assay, the researchers also show that perd interacts genetically with Grip and with multiple edematous wings, which encodes one subunit of the αPS1-βPS integrin that is expressed in tendon cells. These results provide novel insights into how Perd regulates myotube migration and attachment and indicate how integrins function during these processes.
