The segmentation clock in mice: Interaction between the Wnt and Notch signalling pathways

• Published in: Journal of theoretical biology Vol. 248; no. 1; pp. 37 - 47
• Main Authors: Rodríguez-González, J.G., Santillán, M., Fowler, A.C., Mackey, Michael C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.09.2007
• Subjects: Animals; Axin Protein; Biological Clocks; Computational biology; Computer Simulation; Cytoskeletal Proteins - genetics; Embryonic Development - genetics; Gene Expression Regulation, Developmental; Mathematical model; Mice; Models, Biological; Oscillations; Receptor, Notch1 - genetics; Signal Transduction - physiology; Somites - cytology; Somitogenesis; System biology; Time delays; Oscillations; System biology; Time delays; Somitogenesis; Mathematical model; Computational biology
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2007.05.003

In the last few years, the efforts to elucidate the mechanisms underlying the segmentation clock in various vertebrate species have multiplied. Early evidence suggested that oscillations are caused by one of the genes under the Notch signalling pathway (like those of the her or Hes families). Recently, Aulehla et al. [ Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev. Cell 4, 395–406] discovered that Axin2 (a gene under the Wnt3a signalling pathway) also oscillates in the presomitic mesoderm (PSM) of mice embryos and proposed some mechanisms through which the Notch and Wnt3a pathways may interact. They further suggested that a decreasing concentration of Wnt3a along the PSM may be the gradient the segmentation clock interacts with to form somites. These results were reviewed by Rida et al. [A notch feeling of somite segmentation and beyond. Dev. Biol. 265, 2–22], who introduced a complex clockwork comprising genes Hes1, Lfng (under the Notch pathway), and Axin2, as well as their multiple interactions. In the present work we develop a mathematical model based on the Rida et al. review and use it to tackle some of the questions raided by the Aulehla et al. paper: can the Axin2 feedback loop constitute a clock? Could a decreasing Wnt3a signaling constitute the wavefront, where phase is recorded and the spatial pattern laid down? What is the master oscillator?