Acting on identity: Myoblast fusion and the formation of the syncytial muscle fiber

Abstract

The study of Drosophila muscle development dates back to the middle of the last century. Since that time, Drosophila has proved to be an ideal system for studying muscle development, differentiation, function, and disease. As in humans, Drosophila muscle forms via a series of conserved steps, starting with muscle specification, myoblast fusion, attachment to tendon cells, interactions with motorneurons, and sarcomere and myofibril formation. The genes and mechanisms required for these processes share striking similarities to those found in humans. The highly tractable genetic system and imaging approaches available in Drosophila allow for an efficient interrogation of muscle biology and for application of what we learn to other systems. In this article, we review our current understanding of muscle development in Drosophila, with a focus on myoblast fusion, the process responsible for the generation of syncytial muscle cells. We also compare and contrast those genes required for fusion in Drosophila and vertebrates.

RNAi screen inTriboliumreveals involvement of F-BAR proteins in myoblast fusion and visceral muscle morphogenesis in insects

“…Actin polymerization then can further propel membrane curvatures, which in the case of the NOSTRIN, CIP4, and PACSIN family proteins has been reported to promote the formation of filopodia, lamellopodia, podosomes, invadopodia, and to stimulate endocytosis (Chen et al 2012;Liu et al 2015;Salzer et al 2017). Cellular events with these characteristics are also known to be hallmarks during Drosophila myoblast fusion, particularly in fusion-competent myoblasts, in which Dm-Nostrin is expressed (Önel and Renkawitz-Pohl 2009;Kim et al 2015;Deng et al 2017). Thus, during the earliest steps of myoblast fusion, fusion-competent myoblasts extend filopodia to the muscle founder cells before attaching to them (Ruiz-Gomez et al 2000).…”

“…Thus, during the earliest steps of myoblast fusion, fusion-competent myoblasts extend filopodia to the muscle founder cells before attaching to them (Ruiz-Gomez et al 2000). The actual fusion process is driven to a large part by the formation of a dense F-actin focus surrounded by a fusionrestricted myogenic-adhesive structure (FuRMAS) in fusion-competent myoblasts, which propels an invadopodia-like membrane protrusion into the attached founder myoblast or nascent myotube (Önel and Renkawitz-Pohl 2009;Kim et al 2015;Deng et al 2017). This process is thought to provide the key force for membrane rupture and cell fusion (Sens et al 2010) (Önel and Renkawitz-Pohl 2009;Kim et al 2015;Brinkmann et al 2016;Deng et al 2017).…”

“…The actual fusion process is driven to a large part by the formation of a dense F-actin focus surrounded by a fusionrestricted myogenic-adhesive structure (FuRMAS) in fusion-competent myoblasts, which propels an invadopodia-like membrane protrusion into the attached founder myoblast or nascent myotube (Önel and Renkawitz-Pohl 2009;Kim et al 2015;Deng et al 2017). This process is thought to provide the key force for membrane rupture and cell fusion (Sens et al 2010) (Önel and Renkawitz-Pohl 2009;Kim et al 2015;Brinkmann et al 2016;Deng et al 2017). As our data demonstrate a contribution of F-BAR proteins, particularly Nostrin and Cip4, to the process of myoblast fusion, it is conceivable that these proteins provide an additional, perhaps receptor-independent link between the plasma membrane and actin polymerization at the fusion site within fusion-competent myoblasts.…”

The Crk adapter protein is essential forDrosophilaembryogenesis, where it regulates multiple actin-dependent morphogenic events

“…Much of this analysis has focused on roles of Crk in mediating Dock180/ELMO/Rac1 signaling to the actin cytoskeleton via WASP, SCAR, and the Arp2/3 complex (reviewed in Deng et al, 2017).…”

Expression of Hbs, Kirre, and Rst during Drosophila ovarian development

“…In contrast, the cytoplasmic domains of all four proteins are highly divergent with very few conserved regions between them. Their behavior as a partly redundant functional unit mediating selective cell recognition has been established in a variety of developmental contexts, including axonal pathfinding in the optic lobe (Sugie et al, ), cell sorting in the pupal retina (Bao et al, ; Machado et al, ), sensory organ spacing (Reddy et al, ; Linneweber et al, ), and especially during development of the embryonic somatic musculature, where heterophilic interactions between Rst and Hbs, and Kirre and Sns are crucial for myoblast fusion to occur (Abmayr & Pavlath, ; Deng et al, ). Surprisingly, little attention has been paid so far to the role played by IRM components, especially Rst, in ovarian development and oogenesis since it has long been known that some rst mutant alleles are also female sterile (Lefèvre & Green, ; Boschert et al, ; Machado et al, ).…”