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Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior

Overview of attention for article published in BMC Systems Biology, October 2007
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59 Mendeley
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Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior
Published in
BMC Systems Biology, October 2007
DOI 10.1186/1752-0509-1-46
Pubmed ID

Scott H Robertson, Chris K Smith, Anna L Langhans, Sara E McLinden, Matthew A Oberhardt, Karoly R Jakab, Bette Dzamba, Douglas W DeSimone, Jason A Papin, Shayn M Peirce


Tissue morphogenesis is a complex process whereby tissue structures self-assemble by the aggregate behaviors of independently acting cells responding to both intracellular and extracellular cues in their environment. During embryonic development, morphogenesis is particularly important for organizing cells into tissues, and although key regulatory events of this process are well studied in isolation, a number of important systems-level questions remain unanswered. This is due, in part, to a lack of integrative tools that enable the coupling of biological phenomena across spatial and temporal scales. Here, we present a new computational framework that integrates intracellular signaling information with multi-cell behaviors in the context of a spatially heterogeneous tissue environment. We have developed a computational simulation of mesendoderm migration in the Xenopus laevis explant model, which is a well studied biological model of tissue morphogenesis that recapitulates many features of this process during development in humans. The simulation couples, via a JAVA interface, an ordinary differential equation-based mass action kinetics model to compute intracellular Wnt/beta-catenin signaling with an agent-based model of mesendoderm migration across a fibronectin extracellular matrix substrate. The emergent cell behaviors in the simulation suggest the following properties of the system: maintaining the integrity of cell-to-cell contact signals is necessary for preventing fractionation of cells as they move, contact with the Fn substrate and the existence of a Fn gradient provides an extracellular feedback loop that governs migration speed, the incorporation of polarity signals is required for cells to migrate in the same direction, and a delicate balance of integrin and cadherin interactions is needed to reproduce experimentally observed migratory behaviors. Our computational framework couples two different spatial scales in biology: intracellular with multicellular. In our simulation, events at one scale have quantitative and dynamic impact on events at the other scale. This integration enables the testing and identification of key systems-level hypotheses regarding how signaling proteins affect overall tissue-level behavior during morphogenesis in an experimentally verifiable system. Applications of this approach extend to the study of tissue patterning processes that occur during adulthood and disease, such as tumorgenesis and atherogenesis.

Mendeley readers

The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 3%
Japan 1 2%
Belgium 1 2%
United States 1 2%
Luxembourg 1 2%
Unknown 53 90%

Demographic breakdown

Readers by professional status Count As %
Researcher 21 36%
Student > Ph. D. Student 14 24%
Professor 9 15%
Professor > Associate Professor 7 12%
Other 2 3%
Other 5 8%
Unknown 1 2%
Readers by discipline Count As %
Agricultural and Biological Sciences 31 53%
Biochemistry, Genetics and Molecular Biology 8 14%
Computer Science 5 8%
Engineering 3 5%
Chemical Engineering 2 3%
Other 7 12%
Unknown 3 5%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 May 2015.
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