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The Wnt3a/beta-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program

  1. Author:
    Chalamalasetty, R. B.
    Dunty, W. C.
    Biris, K. K.
    Ajima, R.
    Iacovino, M.
    Beisaw, A.
    Feigenbaum, L.
    Chapman, D. L.
    Yoon, J. K.
    Kyba, M.
    Yamaguchi, T. P.

  2. Author Address

    [Chalamalasetty, RB; Dunty, WC; Biris, KK; Ajima, R; Beisaw, A; Yamaguchi, TP] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Iacovino, M; Kyba, M] Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN 55455 USA. [Iacovino, M; Kyba, M] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Feigenbaum, L] NCI, Lab Anim Sci Program, Frederick, MD 21702 USA. [Chapman, DL] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. [Yoon, JK] Maine Med Ctr, Ctr Mol Med, Res Inst, Scarborough, ME 04074 USA.;Yamaguchi, TP (reprint author), NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA;yamagute@mail.nih.gov
    1. Year: 2011
    2. Date: Jul
  2. Journal: Nature Communications
    1. 2
    2. Pages: 12
  4. Type of Article: Article
  5. Article Number: 390
  6. ISSN: 2041-1723
  1. Abstract:

    Segmentation is an organizing principle of body plans. The segmentation clock, a molecular oscillator best illustrated by the cyclic expression of Notch signalling genes, controls the periodic cleavage of somites from unsegmented presomitic mesoderm during vertebrate segmentation. Wnt3a controls the spatiotemporal expression of cyclic Notch genes; however, the underlying mechanisms remain obscure. Here we show by transcriptional profiling of Wnt3a(-/-) embryos that the bHLH transcription factor, Mesogenin1 (Msgn1), is a direct target gene of Wnt3a. To identify Msgn1 targets, we conducted genome-wide studies of Msgn1 activity in embryonic stem cells. We show that Msgn1 is a major transcriptional activator of a Notch signalling program and synergizes with Notch to trigger clock gene expression. Msgn1 also indirectly regulates cyclic genes in the Fgf and Wnt pathways. Thus, Msgn1 is a central component of a transcriptional cascade that translates a spatial Wnt3a gradient into a temporal pattern of clock gene expression.

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  2. DOI: 10.1038/ncomms1381
  3. View record in Web of Science®
  4. WOS: 000294805300017

Library Notes

  1. Fiscal Year: FY2010-2011
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