Spatial Patterning from an Integrated Wnt/β-catenin and Notch/Delta Gene Circuit.
Classically, the Wnt/β-catenin and Notch /Delta signaling pathways were thought to operate through separate mechanisms, performing distinct roles in tissue patterning. However, it has been shown that b-catenin activates transcription of Hesl, a signaling intermediate in the Notch /Delta pathway that controls its lateral inhibition mechanism. To investigate this non-canonical crosstalk mechanism, a new gene circuit, integrating the two pathways, is proposed and simulated in two-cell and multi-cell environments. This model also captures both Paneth cell- mediated and mesenchymal Wnt production. The simulations verify that the gene circuit is temporally bistable and capable of forming a pattern on a multi-cell grid. Last, the model exhibits a bifurcation based on the steady state concentration of Wnt and the relative amount of control b-catenin has over the Hesl promoter, providing a possible mechanism to explain why a homogeneous population of transit amplifying cells is observed directly above the more diverse stem niche.
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Related Subject Headings
- Wnt Signaling Pathway
- Transcription Factor HES-1
- Receptors, Notch
- Promoter Regions, Genetic
- Paneth Cells
- Models, Biological
- Humans
- Gene Regulatory Networks
- Computer Simulation
Citation
Published In
DOI
EISSN
Publication Date
Volume
Start / End Page
Location
Related Subject Headings
- Wnt Signaling Pathway
- Transcription Factor HES-1
- Receptors, Notch
- Promoter Regions, Genetic
- Paneth Cells
- Models, Biological
- Humans
- Gene Regulatory Networks
- Computer Simulation