ArticleMolecular systems biology2015
Data-driven modelling of a gene regulatory network for cell fate decisions in the growing limb bud.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Development of whole-limb skeletal patterning through the coordination of growth and self-organization models.PLoS computational biology · 2026Article
- LimbNET: collaborative platform for simulating spatial patterns of gene networks in limb development.Molecular systems biology · 2026Article
- Advancing developmental biology in Central Europe: report from the V4SDB meeting 2025.Biology open · 2025Article
- Retinoic acid breakdown is required for proximodistal positional identity during axolotl limb regeneration.Nature communications · 2025Article
- Development necessitates evolutionarily conserved factors.Scientific reports · 2025Article
- Spatio-temporal reconstruction of gene expression patterns in developing mice.Development (Cambridge, England) · 2025Article
- Mechanistic regulation of planarian shape during growth and degrowth.Development (Cambridge, England) · 2024Article
- A hybrid physics-based and data-driven framework for cellular biological systems: Application to the morphogenesis of organoids.iScience · 2023Article
- The identifiability of gene regulatory networks: the role of observation data.Journal of biological physics · 2022Article
- Computational Systems Biology of Morphogenesis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Accessible chromatin reveals regulatory mechanisms underlying cell fate decisions during early embryogenesis.Scientific reports · 2021Article
- Computational Stem Cell Biology: Open Questions and Guiding Principles.Cell stem cell · 2021Review
- Retinoid signaling in skeletal development: Scoping the system for predictive toxicology.Reproductive toxicology (Elmsford, N.Y.) · 2021Review
- Adapting machine-learning algorithms to design gene circuits.BMC bioinformatics · 2019Article
- Spatiotemporal control and modeling of morphogen delivery to induce gradient patterning of stem cell differentiation using fluidic channels.Biomaterials science · 2019Article
- Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data.Journal of the Royal Society, Interface · 2018Article
- Modeling craniofacial development reveals spatiotemporal constraints on robust patterning of the mandibular arch.PLoS computational biology · 2018Article
- Calcium as a signal integrator in developing epithelial tissues.Physical biology · 2018Review
- Programming Morphogenesis through Systems and Synthetic Biology.Trends in biotechnology · 2018Review
- Network Features and Dynamical Landscape of Naive and Primed Pluripotency.Biophysical journal · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parameter optimization coupled with model selection is a convenient approach to infer gene regulatory networks from experimental gene expression data, but so far it has been limited to single cells or static tissues where growth is not significant. Here, we present a computational study in which we determine an optimal gene regulatory network from the spatiotemporal dynamics of gene expression patterns in a complex 2D growing tissue (non-isotropic and heterogeneous growth rates). We use this method to predict the regulatory mechanisms that underlie proximodistal (PD) patterning of the developing limb bud. First, we map the expression patterns of the PD markers Meis1, Hoxa11 and Hoxa13 into a dynamic description of the tissue movements that drive limb morphogenesis. Secondly, we use reverse-engineering to test how different gene regulatory networks can interpret the opposing gradients of fibroblast growth factors (FGF) and retinoic acid (RA) to pattern the PD markers. Finally, we validate and extend the best model against various previously published manipulative experiments, including exogenous application of RA, surgical removal of the FGF source and genetic ectopic expression of Meis1. Our approach identifies the most parsimonious gene regulatory network that can correctly pattern the PD markers downstream of FGF and RA. This network reveals a new model of PD regulation which we call the "crossover model", because the proximal morphogen (RA) controls the distal boundary of Hoxa11, while conversely the distal morphogens (FGFs) control the proximal boundary.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.