Drosophila Myoblast Fusion: Invasion and Resistance for the Ultimate Union

Abstract

Cell-cell fusion is indispensable for creating life and building syncytial tissues and organs. Ever since the discovery of cell-cell fusion, how cells join together to form zygotes and multinucleated syncytia has remained a fundamental question in cell and developmental biology. In the past two decades, Drosophila myoblast fusion has been used as a powerful genetic model to unravel mechanisms underlying cell-cell fusion in vivo. Many evolutionarily conserved fusion-promoting factors have been identified and so has a surprising and conserved cellular mechanism. In this review, we revisit key findings in Drosophila myoblast fusion and highlight the critical roles of cellular invasion and resistance in driving cell membrane fusion.

Keywords: Drosophila genetics; actin-propelled membrane protrusions; asymmetric fusogenic synapse; cell–cell fusion; mechanical tension; mechanosensory response; myoblast fusion.

Figure 1

Milestones in the study of Drosophila myoblast fusion. (a) Multinucleated muscle cells visualized in Drosophila embryo (9). (b) Founder cells identified (106). (c) Cell adhesion molecules discovered (18, 104). (d) Discovery of actin-enriched structure (actin focus) at the site of myoblast fusion (76, 79, 100). (e) Discovery of the asymmetric fusogenic synapse (114). (f) Discovery of the role of mechanical tension in promoting myoblast fusion (78).

Figure 2

The asymmetric fusogenic synapse. (a) Molecular components and signaling pathways at the fusogenic synapse. Scar, Arp2/3 complex, Loner, Arf, Sing, and PIP2 are shown once in the two founder cell boxes for the sake of simplicity. (b) Invasive protrusions at the fusogenic synapse visualized by transmission electron microscopy. A mononucleated FCM (pink) is projecting membrane protrusions into the binucleated myotube. Note the exclusion of ribosomes and intracellular organelles in the protrusive area, which is filled with actin filaments. Panel b adapted from Reference with permission. (c) The spectrin network constricts the invasive protrusions, visualized by superresolution microscopy. Actin-propelled protrusions (green) from the FCM penetrate through microdomains free of accumulated β_H-spectrin (red) in the apposing founder cell. Panel c adapted from Reference with permission. Abbreviations: Arf, ADP-ribosylation factor; Arp2/3, actin-related protein 2/3; β_H, βHeavy; Blow, Blown fuse; Crk, Crk oncogene; Dia, Diaphanous; Dock, Dreadlocks; DPak, Drosophila p21-activated kinase; Drk, Downstream of receptor kinase; Duf, Dumbfounded; Elmo, Engulfment and cell motility protein; FCM, fusion-competent myoblast; Hbs, Hibris; Mbc, Myoblast city; MyoII, Myosin II; PIP2, phosphatidylinositol 4,5-bisphosphate; Rok, Rho kinase; Rols, Rolling pebbles; Rst, Roughest; Scar, Suppresser of cAMP receptor/WAVE; Sing, Singles bar; Sns, Sticks and stones; Sltr, Solitary/WIP; WASP, Wiskott–Aldrich syndrome protein; WAVE, WASP family verprolin homologs; WIP, WASP-interacting protein.