Spatial and functional restriction of regulatory molecules during mammalian myoblast fusion

Abstract

Myoblast fusion is a highly regulated process that is key for forming skeletal muscle during development and regeneration in mammals. Much remains to be understood about the molecular regulation of myoblast fusion. Some molecules that influence mammalian muscle fusion display specific cellular localization during myogenesis. Such molecules can be localized to the contact region between two fusing cells either in both cells or only in one of the cells. How distinct localization of molecules contributes to fusion is not clear. Further complexity exists as other molecules are functionally restricted to myoblasts at later stages of myogenesis to regulate their fusion with multinucleated myotubes. This review examines these three categories of molecules and discusses how spatial and functional restriction may contribute to the formation of a multinucleated cell. Understanding how and why molecules become restricted in location or function is likely to provide further insights into the mechanisms regulating mammalian muscle fusion.

Figure 1. Myoblast fusion is associated with spatial and functional localization of molecules

A) Myoblasts proliferate and then, in response to environmental cues, differentiate to become fusion-competent. Myoblast fusion occurs in two stages: in the first phase, a subset of differentiated myoblasts fuse together to form a nascent myotube with a limited number of nuclei. Subsequently, additional differentiated myoblasts fuse with a nascent myotube to generate a large, mature myotube with many nuclei. B) During fusion, myogenic cells are closely juxtaposed. Two differentiated myoblasts are shown here. Some molecules that influence fusion are localized to the contact region between the two cells either in both cells (symmetrical localization) or only in one of the cells (asymmetrical localization). C) Some molecules that influence fusion are only functionally required in differentiated myoblasts as they fuse with nascent myotubes. This is an example of functional localization.