Cross-talk between Hippo and Wnt signalling pathways in intestinal crypts: Insights from an agent-based model

Ward, Daniel; Olivas, Sandra Montes; Fletcher, Alexander G.; Homer, Martin; Marucci, Lucia

doi:10.1016/j.csbj.2019.12.015

Cited by 16 publications

(12 citation statements)

References 67 publications

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“…Discrete cell-based models-independent of being on-or off-lattice-can be coupled to PDE models for simulating the concentration of chemical compounds in the cellular environment or even an ODE model for simulating intracellular dynamics (Cilfone et al 2015;Macklin et al 2016;Ward et al 2020). An extensive review of cell-based models for general tissue mechanics can be found in Van Liedekerke et al (2015).…”

Section: Introductionmentioning

confidence: 99%

Impact of Force Function Formulations on the Numerical Simulation of Centre-Based Models

et al. 2020

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Centre-based or cell-centre models are a framework for the computational study of multicellular systems with widespread use in cancer modelling and computational developmental biology. At the core of these models are the numerical method used to update cell positions and the force functions that encode the pairwise mechanical interactions of cells. For the latter, there are multiple choices that could potentially affect both the biological behaviour captured, and the robustness and efficiency of simulation. For example, available open-source software implementations of centre-based models rely on different force functions for their default behaviour and it is not straightforward for a modeller to know if these are interchangeable. Our study addresses this problem and contributes to the understanding of the potential and limitations of three popular force functions from a numerical perspective. We show empirically that choosing the force parameters such that the relaxation time for two cells after cell division is consistent between different force functions results in good agreement of the population radius of a two-dimensional monolayer relaxing mechanically after intense cell proliferation. Furthermore, we report that numerical stability is not sufficient to prevent unphysical cell trajectories following cell division, and consequently, that too large time steps can cause geometrical differences at the population level.

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Section: Introductionmentioning

confidence: 99%

Impact of Force Function Formulations on the Numerical Simulation of Centre-Based Models

et al. 2020

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“…A comprehensive list of published simulation studies that deal with or include the Wnt signaling pathway is found in Table 1 . Out of the 31 simulation studies ([ 28 – 58 ]), which we have found, we have chosen to collect provenance information from 19 studies, shown in bold in Table 1 . Some of these Wnt models have already been discussed in previous reviews [ 23 , 59 ].…”

Section: Methodsmentioning

confidence: 99%

Relating simulation studies by provenance—Developing a family of Wnt signaling models

et al. 2021

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For many biological systems, a variety of simulation models exist. A new simulation model is rarely developed from scratch, but rather revises and extends an existing one. A key challenge, however, is to decide which model might be an appropriate starting point for a particular problem and why. To answer this question, we need to identify entities and activities that contributed to the development of a simulation model. Therefore, we exploit the provenance data model, PROV-DM, of the World Wide Web Consortium and, building on previous work, continue developing a PROV ontology for simulation studies. Based on a case study of 19 Wnt/β-catenin signaling models, we identify crucial entities and activities as well as useful metadata to both capture the provenance information from individual simulation studies and relate these forming a family of models. The approach is implemented in WebProv, a web application for inserting and querying provenance information. Our specialization of PROV-DM contains the entities Research Question, Assumption, Requirement, Qualitative Model, Simulation Model, Simulation Experiment, Simulation Data, and Wet-lab Data as well as activities referring to building, calibrating, validating, and analyzing a simulation model. We show that most Wnt simulation models are connected to other Wnt models by using (parts of) these models. However, the overlap, especially regarding the Wet-lab Data used for calibration or validation of the models is small. Making these aspects of developing a model explicit and queryable is an important step for assessing and reusing simulation models more effectively. Exposing this information helps to integrate a new simulation model within a family of existing ones and may lead to the development of more robust and valid simulation models. We hope that our approach becomes part of a standardization effort and that modelers adopt the benefits of provenance when considering or creating simulation models.

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“…Hippo and Wnt signaling are closely linked to each other[ 63 ]. YAP1 increases the transcriptional activity of β-catenin, while active Hippo signaling leads to the formation of the destruction complex of Wnt signaling[ 64 , 65 ].…”

Section: The Complex Regulation Network Of Wnt Signalingmentioning

confidence: 99%

Intestinal Wnt in the transition from physiology to oncology

Swoboda¹,

Mittelsdorf²,

Chen³

et al. 2022

WJCO

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Adult stem cells are necessary for self-renewal tissues and regeneration after damage. Especially in the intestine, which self-renews every few days, they play a key role in tissue homeostasis. Therefore, complex regulatory mechanisms are needed to prevent hyperproliferation, which can lead in the worst case to carcinogenesis or under-activation of stem cells, which can result in dysfunctional epithelial. One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway. It is a highly conserved pathway, with β-catenin, a transcription factor, as target protein. Translocation of β-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripo-tency, proliferation, cell differentiation and regulation of cell death. This review presents a brief overview of the Wnt/β-catenin signaling pathway, the regulatory mechanism of this pathway and its role in intestinal homeostasis. Additionally, this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation. Furthermore, the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.

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Cross-talk between Hippo and Wnt signalling pathways in intestinal crypts: Insights from an agent-based model

Abstract: Graphical abstract

Cited by 16 publications

References 67 publications

Impact of Force Function Formulations on the Numerical Simulation of Centre-Based Models

Impact of Force Function Formulations on the Numerical Simulation of Centre-Based Models

Relating simulation studies by provenance—Developing a family of Wnt signaling models

Intestinal Wnt in the transition from physiology to oncology

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