An agent-based model of the Notch signaling pathway elucidates three levels of complexity in the determination of developmental patterning

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Abstract
  • Background: The Notch signaling pathway is involved in cell fate decision and developmental patterning in
    diverse organisms. A receptor molecule, Notch (N), and a ligand molecule (in this case Delta or Dl) are the central
    molecules in this pathway. In early Drosophila embryos, these molecules determine neural vs. skin fates in a
    reproducible rosette pattern.
    Results: We have created an agent-based model (ABM) that simulates the molecular components for this signaling
    pathway as agents acting within a spatial representation of a cell. The model captures the changing levels of these
    components, their transition from one state to another, and their movement from the nucleus to the cell membrane
    and back to the nucleus again. The model introduces stochastic variation into the system using a random generator
    within the Netlogo programming environment. The model uses these representations to understand the biological
    systems at three levels: individual cell fate, the interactions between cells, and the formation of pattern across the
    system. Using a set of assessment tools, we show that the current model accurately reproduces the rosette pattern of
    neurons and skin cells in the system over a wide set of parameters. Oscillations in the level of the N agent eventually
    stabilize cell fate into this pattern. We found that the dynamic timing and the availability of the N and Dl agents in
    neighboring cells are central to the formation of a correct and stable pattern. A feedback loop to the production of
    both components is necessary for a correct and stable pattern.
    Conclusions: The signaling pathways within and between cells in our model interact in real time to create a spatially
    correct field of neurons and skin cells. This model predicts that cells with high N and low Dl drive the formation of the
    pattern. This model also be used to elucidate general rules of biological self-patterning and decision-making.
TitleAn agent-based model of the Notch signaling pathway elucidates three levels of complexity in the determination of developmental patterning
CreatorPfaffmann, Jeffrey O.
Himmelwright, R.
Sanginiti, C.
Reynolds, Elaine R.
PublisherBMC Systems Biology
Academic DepartmentBiology
Computer Science
DivisionNatural Sciences
OrganizationLafayette College
Date Issued2019
Date Available2019-01-21T16:18:56Z
TypeArticle
LanguageEnglish
KeywordAgent-based modeling
Self-patterning
Notch signaling pathway
Bibliographic CitationReynolds, E. R., et al. (2019) "An agent-based model of the Notch signaling pathway elucidates three levels of complexity in the determination of developmental patterning." BMC Systems Biology 13: 7.
Standard IdentifierDOI 10.1186/s12918-018-0672-9
Handle 10385/2631
Permalinkhttp://hdl.handle.net/10385/2631
Rights Statement Creative Commons - Attribution Creative Commons - Attribution
Rights HoldersPfaffmann, Jeffrey O.
Himmelwright, R.
Sanginiti, C.
Reynolds, Elaine R.
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