Mechanisms of myoblast fusion during muscle development

Abstract

The development and regeneration of skeletal muscles require the fusion of mononulceated muscle cells to form multinucleated, contractile muscle fibers. Studies using a simple genetic model, Drosophila melanogaster, have discovered many evolutionarily conserved fusion-promoting factors in vivo. Recent work in zebrafish and mouse also identified several vertebrate-specific factors required for myoblast fusion. Here, we integrate progress in multiple in vivo systems and highlight conceptual advance in understanding how muscle cell membranes are brought together for fusion. We focus on the molecular machinery at the fusogenic synapse and present a three-step model to describe the molecular and cellular events leading to fusion pore formation.

Cell behaviors and dynamics during angiogenesis

“…While cell-cell fusion is a prominent process during development and occurs during the fusion of gametes, the generation of multinucleate muscle fibers and during placenta formation (Aguilar et al, 2013;Demonbreun et al, 2015;Kim et al, 2015;Pérez-Vargas et al, 2014;Podbilewicz, 2014), cell self-fusion is a much rarer phenomenon, but has been well described in C. elegans (Rasmussen et al, 2008). Since, in these particular cases, cells fuse with themselves (as illustrated in Fig.…”

Keep Your Friends Close: Cell–Cell Contact and Skeletal Myogenesis

“…Led by genetic screens in Drosophila and followed by studies in zebrafish and mice, great progress has been made in understanding mechanisms of myoblast fusion. A recent model proposes that three steps underlie myoblast fusion: (1) cell recognition and adhesion, (2) enhancement of cell proximity via F-actin-propelled membrane protrusions by one fusion partner cell and myosin II-dependent cortical tension in the other, and (3) destabilization of the two apposed plasma membrane lipid bilayers and formation of a fusion pore (Kim et al 2015). Many intracellular components that mediate steps 2 and 3 have been identified in Drosophila and, where tested, appear to be evolutionarily conserved in zebrafish and mice, and cultured cells.…”

“…In contrast, a clear picture of the factors that mediate cell recognition and adhesion in these different models has not yet emerged. Comprehensive reviews have recently been published on myoblast fusion (Abmayr and Pavlath 2012;Hindi et al 2013;Kim et al 2015), and for the purposes of this review, we will focus on open questions pertaining to the cell -cell adhesion molecules involved in this process.…”

“…All of these are Ig superfamily receptors (Kim et al 2015). Engagement of these cell adhesion molecules triggers signaling events, which ultimately promote steps 2 and 3 above.…”

Kel1p Mediates Yeast Cell Fusion Through a Fus2p- and Cdc42p-Dependent Mechanism

“…In mammals, these include sperm-egg fusion during fertilization (Wassarman and Litscher 2008), placental trophoblast fusion during pregnancy (Huppertz and Borges 2008), and the fusion of myoblasts to form myofibers during skeletal muscle development (Kim et al 2015). Blocks in placental trophoblast fusion have been correlated with preeclampsia during pregnancy (Gauster et al 2009).…”