Regulation of the Growth of Multinucleated Muscle Cells by an Nfatc2-Dependent Pathway

• Type of Material: Article
• Authors: Valerie Horsley, Emory University; Bret B. Friday, Emory University; Sarah Matteson, Emory University; Kristy Miller Kegley, Emory University; Jonathan Gephart, Emory University; Grace K Pavlath, Emory University
• Language: English
• Date: 2001-04-16
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2001 The Rockefeller University Press
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://jcb.rupress.org/content/153/2/329.full
• Title of Journal or Parent Work: Journal of Cell Biology
• ISSN: 0021-9525
• Volume: 153
• Issue: 2
• Start Page: 329
• End Page: 338
• Grant/Funding Information: This work was supported by National Institutes of Health grants DE11987, DE13040, and AR43410 to G.K. Pavlath.
• Keywords: fusion; myotube; muscle growth; nuclear number; NFATC2
• Research Categories: Health Sciences, Pharmacology; Biology, Cell

Abstract

The nuclear factor of activated T cells (NFAT) family of transcription factors regulates the development and differentiation of several tissue types. Here, we examine the role of NFATC2 in skeletal muscle by analyzing adult NFATC2−/− mice. These mice exhibit reduced muscle size due to a decrease in myofiber cross-sectional area, suggesting that growth is blunted. Muscle growth was examined during regeneration after injury, wherein NFATC2-null myofibers form normally but display impaired growth. The growth defect is intrinsic to muscle cells, since the lack of NFATC2 in primary muscle cultures results in reduced cell size and myonuclear number in myotubes. Retroviral-mediated expression of NFATC2 in the mutant cells rescues this cellular phenotype. Myonuclear number is similarly decreased in NFATC2−/− mice. Taken together, these results implicate a novel role for NFATC2 in skeletal muscle growth. We demonstrate that during growth of multinucleated muscle cells, myoblasts initially fuse to form myotubes with a limited number of nuclei and that subsequent nuclear addition and increases in myotube size are controlled by a molecular pathway regulated by NFATC2.