Patterns of mesenchymal condensation in a multiscale, discrete stochastic model

Cells of the embryonic vertebrate limb in high-density culture undergo chondrogenic pattern formation, which results in the production of regularly spaced "islands" of cartilage similar to the cartilage primordia of the developing limb skeleton. The first step in this process, in vitro and...

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Bibliographic Details
Published in:PLoS computational biology 2007-04, Vol.3 (4), p.e76-e76
Main Authors: Christley, Scott, Alber, Mark S, Newman, Stuart A
Format: Article
Language:English
Subjects:
Animals
Body Patterning - physiology
Cartilage - cytology
Cartilage - growth & development
Cell Differentiation
Chicken
Chondrocytes - cytology
Chondrocytes - physiology
Chondrogenesis - physiology
Computational Biology
Computer Simulation
Condensation
Developmental Biology
Extracellular Matrix - physiology
Humans
In Vitro
Learning models (Stochastic processes)
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - physiology
Models, Biological
Models, Statistical
Morphogenesis - physiology
Programming languages
Stem cell research
Stochastic Processes
Studies
Vertebrates
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Summary:Cells of the embryonic vertebrate limb in high-density culture undergo chondrogenic pattern formation, which results in the production of regularly spaced "islands" of cartilage similar to the cartilage primordia of the developing limb skeleton. The first step in this process, in vitro and in vivo, is the generation of "cell condensations," in which the precartilage cells become more tightly packed at the sites at which cartilage will form. In this paper we describe a discrete, stochastic model for the behavior of limb bud precartilage mesenchymal cells in vitro. The model uses a biologically motivated reaction-diffusion process and cell-matrix adhesion (haptotaxis) as the bases of chondrogenic pattern formation, whereby the biochemically distinct condensing cells, as well as the size, number, and arrangement of the multicellular condensations, are generated in a self-organizing fashion. Improving on an earlier lattice-gas representation of the same process, it is multiscale (i.e., cell and molecular dynamics occur on distinct scales), and the cells are represented as spatially extended objects that can change their shape. The authors calibrate the model using experimental data and study sensitivity to changes in key parameters. The simulations have disclosed two distinct dynamic regimes for pattern self-organization involving transient or stationary inductive patterns of morphogens. The authors discuss these modes of pattern formation in relation to available experimental evidence for the in vitro system, as well as their implications for understanding limb skeletal patterning during embryonic development.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.0030076