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

Abstract

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?

Modelling Oscillator Synchronisation During Vertebrate Axis Segmentation

“…Recent models have tended to utilise the increasing knowledge of molecular regulation of the clock (e.g. [10][11][12][13][14]). However, given incomplete knowledge of the governing molecular networks, the seemingly intricate relationship between oscillator coupling and the molecular clocks, and the difficulty in unambiguously parameterising the current models, coarse-grained descriptions of molecular oscillators have recently been considered in which progression through the somitogenesis clock cycle is described by a single variable -the oscillator phase [15][16][17].…”

Mathematical modelling and experiments for the proliferation and differentiation ofDrosophilaintestinal stem cells I

“…Recently, by using ODE models Goldbeter and Pourquié and Rodríguez-González et al [7,21] theoretically studied interactions between the Wnt and Notch signalling pathways in an oscillator known as the segmentation clock, which controls the formation of somites in the course of vertebrate segmentation.…”

Random cell movement promotes synchronization of the segmentation clock

“…In the PSM, oscillatory expressions are synchronized among neighboring cells. This synchronized oscillation is necessary for normal segmentation, and disruption of the synchronization results in a defective somite boundary (11-13).Theoretical models of segmentation in vertebrates have been developed to explain the spatiotemporal periodicity of the segmentation process (14-18), the oscillatory expression of segmentation clock genes (19)(20)(21)(22)(23)(24), and the wave-like gene expression observed in the anterior PSM (23,(25)(26)(27)(28)(29). Previous theoretical studies have also addressed mechanisms of synchronization of the segmentation clock between cells (13,24,25,30).…”