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Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling

Author

Listed:
  • Yusuke Okubo

    (SOKENDAI
    National Institute of Health Sciences)

  • Takeshi Sugawara

    (Cell Architecture Laboratory, National Institute of Genetics)

  • Natsumi Abe-Koduka

    (National Institute of Genetics)

  • Jun Kanno

    (National Institute of Health Sciences)

  • Akatsuki Kimura

    (Cell Architecture Laboratory, National Institute of Genetics)

  • Yumiko Saga

    (SOKENDAI
    National Institute of Genetics)

Abstract

The synchronized oscillation of segmentation clock is required to generate a sharp somite boundary during somitogenesis. However, the molecular mechanism underlying this synchronization in the mouse embryos is not clarified yet. We used both experimental and theoretical approaches to address this key question. Here we show, using chimeric embryos composed of wild-type cells and Delta like 1 (Dll1)-null cells, that Dll1-mediated Notch signalling is responsible for the synchronization mechanism. By analysing Lunatic fringe (Lfng) chimeric embryos and Notch signal reporter assays using a co-culture system, we further find that Lfng represses Notch activity in neighbouring cells by modulating Dll1 function. Finally, numerical simulations confirm that the repressive effect of Lfng against Notch activities in neighbouring cells can sufficiently explain the synchronization in vivo. Collectively, we provide a new model in which Lfng has a crucial role in intercellular coupling of the segmentation clock through a trans-repression mechanism.

Suggested Citation

  • Yusuke Okubo & Takeshi Sugawara & Natsumi Abe-Koduka & Jun Kanno & Akatsuki Kimura & Yumiko Saga, 2012. "Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2133
    DOI: 10.1038/ncomms2133
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    Cited by:

    1. Benjamin L. Walker & Qing Nie, 2023. "NeST: nested hierarchical structure identification in spatial transcriptomic data," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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