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First published online 14 November 2007
doi: 10.1242/jcs.011668

Journal of Cell Science 120, 4178-4187 (2007)
Published by The Company of Biologists 2007
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Research Article

Functional analysis of homeodomain-containing transcription factor Lbx1 in satellite cells of mouse skeletal muscle

Shuichi Watanabe1, Shunzo Kondo2, Michiko Hayasaka1 and Kazunori Hanaoka1,*

1 Molecular Embryology, Department of Biosciences, School of Science, Kitasato University, Kanagawa, 228-8555, Japan
2 JEOL Ltd, 3-1-2 Musashino, Akishima, Tokyo 196-8558, Japan

* Author for correspondence (e-mail: hanaoka{at}jet.sci.kitasato-u.ac.jp)

Accepted 14 September 2007

Satellite cells are usually mitotically quiescent muscle stem cells, located between the sarcolemma and the basement membrane of muscle fibers. When muscles are damaged, satellite cells become activated, proliferate and differentiate to form multinucleate myofibers. The molecular mechanisms underlying these processes are poorly understood. In the present study, we found that, following treatment with cardiotoxin, homeodomain-containing transcription factor Lbx1 was strongly expressed in the satellite cells of regenerating adult skeletal muscle. Our immunohistochemical and northern blot analyses indicate that Lbx1 is expressed in activated but not quiescent satellite cells. In vitro, this Lbx1 expression was gradually downregulated when satellite cells differentiate into mature myofibers. Transfection and forced expression of Lbx1 in satellite-cell-derived C2C12 myoblast cells resulted in severe depression of myogenic differentiation and incomplete myotube formation, concomitantly with the activation of the paired-box transcription factor Pax7 and depression of the myogenic regulatory factor MyoD. Moreover, knockdown of Lbx1 in in-vitro-cultured satellite cells resulted in downregulation of Pax7. These results suggest that Lbx1 plays important roles in differentiation and maintenance of satellite cells of mature myofibers, probably through the regulation of Pax7.

Key words: Lbx1, Pax7, Satellite cells, Stem cells, Muscle






© The Company of Biologists Ltd 2007