Abstract
We propose a model for the segmentation clock in vertebrate somitogenesis, based on the Wnt signaling pathway. The core of the model is a negative feedback loop centered around the Axin2 protein. Axin2 is activated by β-catenin, which in turn is degraded by a complex of GSK3β and Axin2. The model produces oscillatory states of the involved constituents with typical time periods of a few hours (ultradian oscillations). The oscillations are robust to changes in parameter values and are often spiky, where low concentration values of β-catenin are interrupted by sharp peaks. Necessary for the oscillations is the saturated degradation of Axin2. Somite formation in chick and mouse embryos is controlled by a spatial Wnt gradient which we introduce in the model through a time-dependent decrease in Wnt3a ligand level. We find that the oscillations disappear as the ligand concentration decreases, in agreement with observations on embryos.
| Original language | English |
|---|---|
| Journal | Biophysical Journal |
| Volume | 98 |
| Issue number | 6 |
| Pages (from-to) | 943-950 |
| Number of pages | 8 |
| ISSN | 0006-3495 |
| DOIs | |
| Publication status | Published - 17 Mar 2010 |
Keywords
- Animals
- Biological Clocks
- Computer Simulation
- Embryonic Development
- Humans
- Models, Biological
- Somites
- Wnt Proteins