Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites

Zoltan Ferjentsik, Shinichi Hayashi, J. Kim Dale, Yasumasa Bessho, An Herreman, Bart De Strooper, Gonzalo del Monte, Jose Luis de la Pompa, Miguel Maroto

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    Abstract

    Segmentation of the vertebrate body axis is initiated through somitogenesis, whereby epithelial somites bud off in pairs periodically from the rostral end of the unsegmented presomitic mesoderm (PSM). The periodicity of somitogenesis is governed by a molecular oscillator that drives periodic waves of clock gene expression caudo-rostrally through the PSM with a periodicity that matches somite formation. To date the clock genes comprise components of the Notch, Wnt, and FGF pathways. The literature contains controversial reports as to the absolute role(s) of Notch signalling during the process of somite formation. Recent data in the zebrafish have suggested that the only role of Notch signalling is to synchronise clock gene oscillations across the PSM and that somite formation can continue in the absence of Notch activity. However, it is not clear in the mouse if an FGF/Wnt-based oscillator is sufficient to generate segmented structures, such as the somites, in the absence of all Notch activity. We have investigated the requirement for Notch signalling in the mouse somitogenesis clock by analysing embryos carrying a mutation in different components of the Notch pathway, such as Lunatic fringe (Lfng), Hes7, Rbpj, and presenilin1/presenilin2 (Psen1/Psen2), and by pharmacological blocking of the Notch pathway. In contrast to the fish studies, we show that mouse embryos lacking all Notch activity do not show oscillatory activity, as evidenced by the absence of waves of clock gene expression across the PSM, and they do not develop somites. We propose that, at least in the mouse embryo, Notch activity is absolutely essential for the formation of a segmented body axis.

    Original languageEnglish
    Article numbere1000662
    Pages (from-to)-
    Number of pages14
    JournalPLoS Genetics
    Volume5
    Issue number9
    DOIs
    Publication statusPublished - Sep 2009

    Keywords

    • Cyclic gene expression
    • Segmentation clock
    • Gamma secretase
    • Lunatic fringe
    • Zebrafish somitogenesis
    • Boundary formation
    • Signaling pathway
    • Delta-homolog
    • RBP-J
    • Presenelin

    Cite this

    Ferjentsik, Z., Hayashi, S., Dale, J. K., Bessho, Y., Herreman, A., De Strooper, B., del Monte, G., Luis de la Pompa, J., & Maroto, M. (2009). Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genetics, 5(9), -. [e1000662]. https://doi.org/10.1371/journal.pgen.1000662