Mathematical models for the Notch and Wnt signaling pathways and the crosstalk between them during somitogenesis
Open accessAbstract
Background: Somitogenesis is a fundamental characteristic feature of development in various animal embryos. Molecular evidence has proved that the Notch and Wnt pathways play important roles in regulating the process of somitogenesis and there is crosstalk between these two pathways. However, it is difficult to investigate the detailed mechanism of these two pathways and their interactions in somitogenesis through biological experiments. In recent years some mathematical models have been proposed for the purpose of studying the dynamics of the Notch and Wnt pathways in somitogenesis. Unfortunately, only a few of these models have explored the interactions between them. Results: In this study, we have proposed three mathematical models for the Notch signalling pathway alone, the Wnt signalling pathway alone, and the interactions between them. These models can simulate the dynamics of the Notch and Wnt pathways in somitogenesis, and are capable of reproducing the observations derived from wet experiments. They were used to investigate the molecular mechanisms of the Notch and Wnt pathways and their crosstalk in somitogenesis through the model simulations. Conclusions: Three mathematical models are proposed for the Notch and Wnt pathways and their interaction during somitogenesis. The simulations demonstrate that the extracellular Notch and Wnt signals are essential for the oscillating expressions of both Notch and Wnt target genes. Moreover, the internal negative feedback loops and the three levels of crosstalk between these pathways play important but distinct roles in maintaining the system oscillation. In addition, the results of the parameter sensitivity analysis of the models indicate that the Notch pathway is more sensitive to perturbation in somitogenesis.
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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 [48]
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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Experimental — accuracy not yet measuredSome 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 [48]
The Methods section, “Parameter learning algorithm” (page unavailable), says the authors trained most model parameters using microarray data, supporting the calibration claim. But “just calibrated” is too restrictive: the Results also report parameter-sensitivity analyses and say the Wnt simulation reproduced wet experimental results. (LLM, conf=0.82)
Experimental — accuracy not yet measuredRequirements could only be identified in the publications of Lee et al. (2003) [28], Wang et al. (2013) [48], Chen et al. (2014) [49], and Haack et al. (2020) [56].
“We could only identify Requirements in the publications of Lee et al. (2003) [28], Wang et al. (2013) [48], Chen et al. (2014) [49], and Haack et al. (2020) [56].”
From Relating simulation studies by provenance—Developing a family of Wnt signaling models (2021) · cites this paper as [48]
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 [48]
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 [48]
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- Authors
- Wang, H.-Y., Huang, Y.-X., Qi, Y.-F., Zhang, Y., Bao, Y.-L., Sun, L.-G., Zheng, L.-H., Zhang, Y.-W., Ma, Z.-Q., & Li, Y.-X.
- Affiliations
- Northeast Normal University (CN)
- Venue
- Theoretical Biology and Medical Modelling
- Published
- 2013-04-20
- Volume
- 10
- Issue
- 1
- Pages
- 27-27
- ISSN
- 1742-4682 (ISSN-L)
- PMC
- PMC3648501
- OpenAlex
- W2108654247
- Cited by
- 14
- References
- 36
- Citations by year
- 2026: 1 · 2021: 1 · 2020: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Theoretical Biology and Medical Modelling (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Jilin Province
- National Natural Science Foundation of China (61172183)
- People's Government of Jilin Province
- Fundamental Research Funds for the Central Universities (11QNJJ021)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Notch signaling, Wnt signaling, somitogenesis, pathway crosstalk, mathematical modeling of signaling, gene expression oscillations, negative feedback loop, parameter sensitivity analysis, embryonic development
- MeSH terms
- Animals, Embryo, Nonmammalian, Models, Theoretical, Signal Transduction, Somites, Wnt Proteins, Receptors, Notch
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