reaction_1
Xi expr
∅ > species_1
reaction_2
Xi degr
species_1 > ∅
reaction_3
Yi expr
∅ > species_2
reaction_4
Yi degr
species_2 > ∅
reaction_5
Xj expr
∅ > species_3
reaction_6
Xj degr
species_3 > ∅
reaction_7
Yj expr
∅ > species_4
reaction_8
Yj degr
species_4 > ∅
Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.
On the role of lateral stabilization during early patterning in the pancreas.
J R Soc Interface 2013;
10
(79):
20120766
- PubMed: 23193107
- PubMed Central: PMC3565694
- DOI: 10.1098/rsif.2012.0766
- ISSN: 1742-5662
- URL: https://ncbi.nlm.nih.gov/pubmed/23193107
Abstract
The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell-cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell-cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000435)
Biomodels notes: Figure 3d of the reference publication has been reproduced here. Xi and Xj denote the expression of pro-endocrine transcription factor Ngn3 (neurogenin-3) in cells i and j, respectively. Yi and Yj denote the expression of transcription factor Ptf1a (Pancreas-specific transcription factor 1 subunit alpha) in cells i and j, respectively.
The model was simulated using Copasi v4.8 (Build 35). The plot was generated using Gnuplot.
JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.