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  • Title: The intracellular domain of mouse Notch: a constitutively activated repressor of myogenesis directed at the basic helix-loop-helix region of MyoD.
    Author: Kopan R, Nye JS, Weintraub H.
    Journal: Development; 1994 Sep; 120(9):2385-96. PubMed ID: 7956819.
    Abstract:
    We show that Myf-5 and mNotch mRNA are both present in the presomitic mesoderm before muscle cell commitment and before muscle structural gene activation. The failure of presomitic mesoderm to respond to Myf-5 and express myogenic properties implies that there may be a mechanism in presomitic mesoderm to suppress muscle differentiation. Here we show that ectopic expression of the intracellular domain of mNotch (mNotchIC) functions as a constitutively activated repressor of myogenesis both in cultured cells and in frog embryos. Mutagenesis experiments indicate that the target for inactivation by mNotch is the MyoD basic helix-loop-helix domain. mNotchIC contains a nuclear localization signal and localizes to the nucleus. Removal of the nuclear localization signal (NLS) reduces nuclear localization and diminishes the inhibition of myogenesis caused by Myf-5 or MyoD. Additional experiments show that the CDC10/SWI6/ankyrin repeats are also necessary for myogenic inhibition.
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