BCL9 is an essential component of canonical Wnt signaling that mediates the differentiation of myogenic progenitors during muscle regeneration

Andrew S. Brack, Fabienne Murphy-Seiler, Jasmine Hanifi, Jürgen Deka, Sven Eyckerman, Charles Keller, Michel Aguet, Thomas A. Rando

    Research output: Contribution to journalArticlepeer-review

    68 Scopus citations

    Abstract

    Muscle stem cells and their progeny play a fundamental role in the regeneration of adult skeletal muscle. We have previously shown that activation of the canonical Wnt/β-catenin signaling pathway in adult myogenic progenitors is required for their transition from rapidly dividing transient amplifying cells to more differentiated progenitors. Whereas Wnt signaling in Drosophila is dependent on the presence of the co-regulator Legless, previous studies of the mammalian ortholog of Legless, BCL9 (and its homolog, BCL9-2), have not revealed an essential role of these proteins in Wnt signaling in specific tissues during development. Using Cre-lox technology to delete BCL9 and BCL9-2 in the myogenic lineage in vivo and RNAi technology to knockdown the protein levels in vitro, we show that BCL9 is required for activation of the Wnt/β-catenin cascade in adult mammalian myogenic progenitors. We observed that the nuclear localization of β-catenin and downstream TCF/LEF-mediated transcription, which are normally observed in myogenic progenitors upon addition of exogenous Wnt and during muscle regeneration, were abrogated when BCL9/9-2 levels were reduced. Furthermore, reductions of BCL9/9-2 inhibited the promotion of myogenic differentiation by Wnt and the normal regenerative response of skeletal muscle. These results suggest a critical role of BCL9/9-2 in the Wnt-mediated regulation of adult, as opposed to embryonic, myogenic progenitors.

    Original languageEnglish (US)
    Pages (from-to)93-105
    Number of pages13
    JournalDevelopmental Biology
    Volume335
    Issue number1
    DOIs
    StatePublished - Nov 1 2009

    Keywords

    • BCL9
    • Muscle
    • Myogenesis
    • Satellite cells
    • Wnt

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology
    • Cell Biology

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