Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size

Jennifer R. Knapp, Judith K. Davie, Anita Myer, Eric Meadows, Eric N. Olson, William H. Klein

    Research output: Contribution to journalArticle

    106 Scopus citations

    Abstract

    Although the mechanisms regulating the formation of embryonic skeletal muscle in vertebrates are well characterized, less is known about postnatal muscle formation even though the largest increases in skeletal muscle mass occur after birth. Adult muscle stem cells (satellite cells) appear to recapitulate the events that occur in embryonic myoblasts. In particular, the myogenic basic helix-loop-helix factors, which have crucial functions in embryonic muscle development, are assumed to have similar roles in postnatal muscle formation. Here, we test this assumption by determining the role of the myogenic regulator myogenin in postnatal life. Because Myog-null mice die at birth, we generated mice with floxed alleles of Myog and mated them to transgenic mice expressing Cre recombinase to delete Myog before and after embryonic muscle development. Removing myogenin before embryonic muscle development resulted in myofiber deficiencies identical to those observed in Myog-null mice. However, mice in which Myog was deleted following embryonic muscle development had normal skeletal muscle, except for modest alterations in the levels of transcripts encoding Mrf4 (Myf6) and Myod1 (MyoD). Notably, Myog-deleted mice were 30% smaller than control mice, suggesting that the absence of myogenin disrupted general body growth. Our results suggest that postnatal skeletal muscle growth is controlled by mechanisms distinct from those occurring in embryonic muscle development and uncover an unsuspected non-cell autonomous role for myogenin in the regulation of tissue growth.

    Original languageEnglish (US)
    Pages (from-to)601-610
    Number of pages10
    JournalDevelopment
    Volume133
    Issue number4
    DOIs
    StatePublished - Feb 1 2006

    Keywords

    • Conditional knockout mice
    • Myogenic bHLH transcription factors
    • Myogenin
    • Skeletal muscle growth

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology

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  • Cite this

    Knapp, J. R., Davie, J. K., Myer, A., Meadows, E., Olson, E. N., & Klein, W. H. (2006). Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size. Development, 133(4), 601-610. https://doi.org/10.1242/dev.02249