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.
| Title | An agent-based model of the Notch signaling pathway elucidates three levels of complexity in the determination of developmental patterning |
|---|---|
| Creator | Pfaffmann, Jeffrey O. |
| Himmelwright, R. | |
| Sanginiti, C. | |
| Reynolds, Elaine R. | |
| Publisher | BMC Systems Biology |
| Academic Department | Biology |
| Computer Science | |
| Division | Natural Sciences |
| Organization | Lafayette College |
| Date Issued | 2019 |
| Date Available | 2019-01-21T16:18:56Z |
| Type | Article |
| Language | English |
| Keyword | Agent-based modeling |
| Self-patterning | |
| Notch signaling pathway | |
| Bibliographic Citation | Reynolds, 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 Identifier | DOI 10.1186/s12918-018-0672-9 |
| Handle 10385/2631 | |
| Permalink | http://hdl.handle.net/10385/2631 |
| Rights Statement |
Creative Commons - Attribution
|
| Rights Holders | Pfaffmann, Jeffrey O. |
| Himmelwright, R. | |
| Sanginiti, C. | |
| Reynolds, Elaine R. |
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| File | Reynolds-BMCSystemsBiology-vol13-2019.pdf | Uploaded 2019-10-20 | Public | Download |
| File | Reynolds-BMCSystemsBiology-vol13-2019-s3.csv | Uploaded 2019-10-20 | Public | Download |
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| File | Reynolds-BMCSystemsBiology-vol13-2019-s2.txt | Uploaded 2019-10-20 | Public | Download |
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