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First published online 12 December 2006
doi: 10.1242/jcs.03307

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A combinatorial role for NFAT5 in both myoblast migration and differentiation during skeletal muscle myogenesis

¹ Graduate Program in Molecular and Systems Pharmacology Emory University, Atlanta, GA 30322, USA
² Department of Pharmacology, Emory University, Atlanta, GA 30322, USA
³ Biogen Idec, Inc., San Diego, CA 92122, USA

^* Author for correspondence (e-mail: gpavlat{at}emory.edu)

Accepted 18 October 2006

Skeletal muscle regeneration depends on myoblast migration, differentiation and myofiber formation. Isoforms of the nuclear factor of activated T cells (NFAT) family of transcription factors display nonredundant roles in skeletal muscle. NFAT5, a new isoform of NFAT, displays many differences from NFATc1-c4. Here, we examine the role of NFAT5 in myogenesis. NFAT5^+/- mice displayed a defect in muscle regeneration with fewer myofibers formed at early times after injury. NFAT5 has a muscle-intrinsic function because inhibition of NFAT5 transcriptional activity caused both a migratory and differentiation defect in cultured myoblasts. We identified Cyr61 as a target of NFAT5 signaling in skeletal muscle cells. Addition of Cyr61 to cells expressing inhibitory forms of NFAT5 rescued the migratory phenotype. These results demonstrate a role for NFAT5 in skeletal muscle cell migration and differentiation. Furthermore, as cell-cell interactions are crucial for myoblast differentiation, these data suggest that myoblast migration and differentiation are coupled and that NFAT5 is a key regulator.

Key words: Skeletal muscle, NFAT5, TonEBP, Myogenesis, Migration, Differentiation

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