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?
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The model by Rodríguez-González et al. (2007) [33] lacks β-catenin.
“There are two exceptions: the simulation model by Sick et al. 2006 [31] contains only Wnt and its antagonist Dkk and the model by Rodríguez-González et al. (2007) [33] lacks β-catenin.”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57]).
“Some authors just calibrated their simulation models ([33, 46, 48, 49, 53, 57])”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
All other simulation studies either used wet-lab data from other publications or did not explicitly refer to wet-lab data at all [29, 30, 33, 34, 39, 41, 53].
“All other simulation studies either used wet-lab data from other publications or did not explicitly refer to wet-lab data at all [29, 30, 33, 34, 39, 41, 53].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
A third cluster includes the pathways of Notch [33, 48] and Notch + MAPK/ERK [36].
“A third cluster includes the pathways of Notch [33, 48] and Notch + MAPK/ERK [36].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
The two simulation models not linked to Lee et al. (2003) are those by Sick et al. (2006) and by Rodríguez-González et al. (2007).
“The two exceptions not linked to Lee et al. (2003) [28] are the simulation models by Sick et al. (2006) [31] and by Rodríguez-González et al. (2007) [33].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
Some studies develop a story line where a simulation model has been successively refined, extended, or composed ([28, 33, 34, 36, 41, 46, 48, 49, 51, 56]).
“Some studies develop a story line where a simulation model has been successively refined, extended, or composed ([28, 33, 34, 36, 41, 46, 48, 49, 51, 56]).”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
Some simulation studies resulted in the development of multiple simulation models that are neither extensions nor compositions but rather form a revision or alternative to other simulation models developed in the same study: [33, 39, 41, 46, 48, 49].
“Some simulation studies resulted in the development of multiple simulation models that are neither extensions nor compositions but rather form a revision or alternative to other simulation models developed in the same study: [33, 39, 41, 46, 48, 49].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
Rodríguez-González et al. (2007) consider Wnt and Axin only in the context of the Notch signaling pathway, so their model contains only a fragment of the canonical Wnt pathway.
“Rodríguez-González et al. (2007) consider Wnt and Axin—two key players of the Wnt/β-catenin signaling pathway—but only in the context of the Notch signaling pathway and thus the model only contains a fragment of the canonical Wnt pathway.”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [33]
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References 20 · Cited by 41
- Authors
- Rodríguez-González, J. G., Santillán, M., Fowler, A. C., & Mackey, M. C.
- Affiliations
- Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (MX)
- McGill University (CA)
- University of Oxford (GB)
- Corresponding author
- Santillán, M.
- Venue
- Journal of Theoretical Biology
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 248
- Issue
- 1
- Pages
- 37-47
- ISSN
- 0022-5193 (ISSN-L)
- OpenAlex
- W2126714704
- Cited by
- 41
- References
- 20
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2018: 1 · 2017: 1 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 5
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Theoretical Biology (publishedVersion)
- PubMed (publishedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion)
- Funders
- University of Oxford
- Academia Mexicana de Ciencias
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Physical Sciences › Computer Science › Computer Networks and Communications › Nonlinear Dynamics and Pattern Formation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- segmentation clock, somitogenesis, Wnt3a signaling, Notch signaling, Axin2, presomitic mesoderm, Hes1, Lfng, mathematical model, wavefronts, master oscillator, mouse embryo
- MeSH terms
- Animals, Biological Clocks, Computer Simulation, Cytoskeletal Proteins, Models, Biological, Signal Transduction, Gene Expression Regulation, Developmental, Somites, Embryonic Development, Mice, Receptor, Notch1, Axin Protein
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