Abstract
BackgroundThe 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.ResultsWe 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.ConclusionsThe 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.
Highlights
The Notch signaling pathway is involved in cell fate decision and developmental patterning in diverse organisms
One of the canonical pathways for fate decisions and patterning is the Notch pathway. This pathway is used in multiple tissue types and across evolutionary time; it is the most common pathway used by adjacent cells to make binary fate decisions [1]
Using agent-based model (ABM), we can focus on one product, and add or control effectors in a stepwise fashion to see which are important to the overall patterning
Summary
The Notch signaling pathway is involved in cell fate decision and developmental patterning in diverse organisms. In early Drosophila embryos, these molecules determine neural vs skin fates in a reproducible rosette pattern. The Drosophila early embryo is the best studied Notch pathway, where Notch (N), an extracellular receptor, and its ligand Delta (Dl) act to determine the fate of a sheet of ectodermal cells, with cells adopting either a neuronal or epidermal fate in a reproducible rosette spatial pattern [2, 3]. Cells with (2019) 13:7 high levels of N protein assume an epidermal fate, while a low level of N produces the neuronal fate This signaling pathway yields a reproducible geometry and consistent number of neural and epidermal cells, it is unclear how the identical cellular pathways within each cell interact to create pattern within a group of cells
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