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Published 9 June 2003. doi:10.1083/jcb.200301058
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© The Rockefeller University Press, 0021-9525/2003/6/861 $5.00
The Journal of Cell Biology, Volume 161, Number 5, 861-874

Article

Requirement of transcription factor NFAT in developing atrial myocardium



William Schubert1, Xiao Yong Yang1, Teddy T.C. Yang1, Stephen M. Factor2, Michael P. Lisanti1, Jeffery D. Molkentin3, Mercedes Rincón4 and Chi-Wing Chow1

1 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, NY 10461
2 Department of Pathology and Medicine, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, Bronx, NY 10461
3 Children's Hospital Medical Center, Molecular Cardiovascular Biology Program, Cincinnati, OH 45229
4 Department of Medicine, Immunobiology Program, University of Vermont, Burlington, VT 05401

Address correspondence to Chi-Wing Chow, Dept. of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: (718) 430-2716. Fax: (718) 430-8922. E-mail: cchow{at}aecom.yu.edu

Nuclear factor of activated T cell (NFAT) is a ubiquitous regulator involved in multiple biological processes. Here, we demonstrate that NFAT is temporally required in the developing atrial myocardium between embryonic day 14 and P0 (birth). Inhibition of NFAT activity by conditional expression of dominant-negative NFAT causes thinning of the atrial myocardium. The thin myocardium exhibits severe sarcomere disorganization and reduced expression of cardiac troponin-I (cTnI) and cardiac troponin-T (cTnT). Promoter analysis indicates that NFAT binds to and regulates transcription of the cTnI and the cTnT genes. Thus, regulation of cytoskeletal protein gene expression by NFAT may be important for the structural architecture of the developing atrial myocardium.

Key Words: heart development; cardiac myocytes; inducible transgenic mice; sarcomeric proteins; troponin complex

* Abbreviations used in this paper: {Delta}Cn, constitutive active calcineurin; CsA, cyclosporin A; cTnI, cardiac troponin-I; cTnT, cardiac troponin-T; dnNFAT, dominant-negative NFAT; Dox, doxycycline; E, embryonic day; IL, interleukin; NFAT, nuclear factor of activated T cell; PPAR{gamma}2, peroxisome proliferator–activated receptor {gamma}2; ssTnI, slow skeletal troponin-I; ssTnT, slow skeletal troponin-T; Tg+, transgenic positive; Wt, wild type.


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