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BIOMD0000000435 - deBack2012 - Lineage Specification in Pancreas Development

 

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Reference Publication
Publication ID: 23193107
de Back W, Zhou JX, Brusch L.
On the role of lateral stabilization during early patterning in the pancreas.
J R Soc Interface 2013 Feb; 10(79): 20120766
Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.  [more]
Model
Original Model: BIOMD0000000435.xml.origin
Submitter: Lutz Brusch
Submission ID: MODEL1211010000
Submission Date: 01 Nov 2012 14:21:57 UTC
Last Modification Date: 12 Feb 2013 15:33:48 UTC
Creation Date: 28 Nov 2012 13:53:36 UTC
Encoders:  Vijayalakshmi Chelliah
   Lutz Brusch
set #1
bqbiol:isVersionOf Gene Ontology cell-cell signaling
bqbiol:occursIn Taxonomy Murinae
bqbiol:isPartOf Gene Ontology pancreas development
Notes
deBack2012 - Lineage Specification in Pancreas Development

This model of two neighbouring pancreas precursor cells, describes the exocrine versus endocrine lineage specification process. To account for the tissue scale patterns, this couplet model has been extended to hundreds of coupled cells.

This model is described in the article:

de Back W., Zhou JX, Brusch L
J. R. Soc. Interface 6 February 2013 vol. 10 no. 79 20120766

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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 23193107 Submission Date: 01 Nov 2012 14:21:57 UTC Last Modification Date: 12 Feb 2013 15:33:48 UTC Creation Date: 28 Nov 2012 13:53:36 UTC
Mathematical expressions
Reactions
Xi expr Xi degr Yi expr Yi degr
Xj expr Xj degr Yj expr Yj degr
Physical entities
Compartments Species
compartment Xi Yi Xj
Yj    
Reactions (8)
 
 Xi expr  → [Xi];   {Xj} , {Xj}
 
 Xi degr [Xi] → ;   {Xi}
 
 Yi expr  → [Yi];   {Yi} , {Yj} , {Xi} , {Yi} , {Yj} , {Xi}
 
 Yi degr [Yi] → ;   {Yi}
 
 Xj expr  → [Xj];   {Xi} , {Xi}
 
 Xj degr [Xj] → ;   {Xj}
 
 Yj expr  → [Yj];   {Yi} , {Yj} , {Xj} , {Yi} , {Yj} , {Xj}
 
 Yj degr [Yj] → ;   {Yj}
 
Functions (2)
 
 Lateral inhibition [1] lambda(theta, a, Xj, n, theta/(theta+a*Xj^n))
 
 Lateral stabilisation [1] lambda(theta, b, Yi, Yj, n, c, Xi, (theta+b*(Yi*Yj)^n)/(theta+c*Xi^n+b*(Yi*Yj)^n))
 
 compartment Spatial dimensions: 3.0  Compartment size: 1.0
 
 Xi
Compartment: compartment
Initial concentration: 0.0
 
 Yi
Compartment: compartment
Initial concentration: 0.0
 
 Xj
Compartment: compartment
Initial concentration: 0.0
 
 Yj
Compartment: compartment
Initial concentration: 0.0
 
Xi expr (3)
 
   theta
Value: 1.0E-4
Constant
 
   a
Value: 1.0
Constant
 
   n
Value: 4.0
Constant
 
Xi degr (1)
 
   k1
Value: 1.0
Constant
 
Yi expr (4)
 
   theta
Value: 1.0E-4
Constant
 
   b
Value: 21.0
Constant
 
   n
Value: 4.0
Constant
 
   c
Value: 1.0
Constant
 
Yi degr (1)
 
   k1
Value: 1.0
Constant
 
Xj expr (3)
 
   theta
Value: 1.0E-4
Constant
 
   a
Value: 1.0
Constant
 
   n
Value: 4.0
Constant
 
Xj degr (1)
 
   k1
Value: 1.0
Constant
 
Yj expr (4)
 
   theta
Value: 1.0E-4
Constant
 
   b
Value: 21.0
Constant
 
   n
Value: 4.0
Constant
 
   c
Value: 1.0
Constant
 
Yj degr (1)
 
   k1
Value: 1.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000435

Curator's comment: (updated: 28 Nov 2012 13:51:02 GMT)

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.

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