Abstract
Somatic cell fusion is an essential component of skeletal muscle development and growth and repair from injury. Additional cell types such as trophoblasts and osteoclasts also require somatic cell fusion events to perform their physiological functions. Currently we have rudimentary knowledge on molecular mechanisms regulating somatic cell fusion events in mammals. We therefore investigated during in vitro murine myogenesis a mammalian homolog, Kirrel, of the Drosophila Melanogaster genes Roughest (Rst) and Kin of Irre (Kirre) which regulate somatic muscle cell fusion during embryonic development. Our results demonstrate the presence of a novel murine Kirrel isoform containing a truncated cytoplasmic domain which we term Kirrel B. Protein expression levels of Kirrel B are inverse to the occurrence of cell fusion events during in vitro myogenesis which is in stark contrast to the expression profile of Rst and Kirre during myogenesis in Drosophila. Furthermore, chemical inhibition of cell fusion confirmed the inverse expression pattern of Kirrel B protein levels in relation to cell fusion events. The discovery of a novel Kirrel B protein isoform during myogenesis highlights the need for more thorough investigation of the similarities and potential differences between fly and mammals with regards to the muscle cell fusion process.
Highlights
Generation of the syncytial trophoblast during embryonic development, formation of syncytial skeletal muscle fibers, and development of osteoclasts highlight important developmental processes in mammals which are underpinned by somatic cell fusion events
Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society
We present evidence that expression levels of the Kirrel B protein isoform are surprisingly inverse to occurrence of somatic cell fusion events during in vitro myogenesis which is in stark contrast to the expression profile of Kin of Irre (Kirre) and Rst during myogenesis in Drosophila, whereby their expression is highest when the greatest number of cell fusion events are occurring (Ruiz-Gomez et al 2000; Stru€nkelnberg et al 2001)
Summary
Generation of the syncytial trophoblast during embryonic development, formation of syncytial skeletal muscle fibers, and development of osteoclasts highlight important developmental processes in mammals which are underpinned by somatic cell fusion events. The diverse array of cell types affected by somatic cell fusion events demonstrates the need for intense study of this rudimentary understood process. In specific tissue types, such as skeletal muscle, thousands of cell fusion events can take place during the development of a single human muscle fiber in vivo (Peckham 2008); these fusion events are asynchronous and suggest that the somatic cell fusion process is under temporal control of specific genes. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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