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BIOMD0000000275 - Goldbeter2007_Somitogenesis_Switch

 

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Reference Publication
Publication ID: 17497689
Goldbeter A, Gonze D, Pourquié O.
Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling.
Dev. Dyn. 2007 Jun; 236(6): 1495-1508
Faculté des Sciences, Université Libre de Bruxelles, U.L.B., Brussels, Belgium.  [more]
Model
Original Model: BIOMD0000000275.xml.origin
Submitter: Lukas Endler
Submission ID: MODEL1011170000
Submission Date: 17 Nov 2010 08:31:45 UTC
Last Modification Date: 29 Nov 2011 11:56:05 UTC
Creation Date: 17 Nov 2010 08:39:05 UTC
Encoders:  Lukas Endler
set #1
bqbiol:isVersionOf Gene Ontology somitogenesis
set #2
bqbiol:occursIn Taxonomy Vertebrata
bqbiol:hasVersion Gene Ontology response to retinoic acid
Gene Ontology cellular response to fibroblast growth factor stimulus
Notes

This is the simple model without diffusion described in th epublication
Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling.
Goldbeter A, Gonze D, Pourquié O. Dev Dyn. 2007 Jun;236(6):1495-508. PMID: 17497689 , doi: 10.1016/j.jtbi.2008.01.006
Abstract:
The establishment of thresholds along morphogen gradients in the embryo is poorly understood. Using mathematical modeling, we show that mutually inhibitory gradients can generate and position sharp morphogen thresholds in the embryonic space. Taking vertebrate segmentation as a paradigm, we demonstrate that the antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF) along the presomitic mesoderm (PSM) may lead to the coexistence of two stable steady states. Here, we propose that this bistability is associated with abrupt switches in the levels of FGF and RA signaling, which permit the synchronized activation of segmentation genes, such as mesp2, in successive cohorts of PSM cells in response to the segmentation clock, thereby defining the future segments. Bistability resulting from mutual inhibition of RA and FGF provides a molecular mechanism for the all-or-none transitions assumed in the "clock and wavefront" somitogenesis model. Given that mutually antagonistic signaling gradients are common in development, such bistable switches could represent an important principle underlying embryonic patterning.

Originally created by libAntimony v1.4 (using libSBML 3.4.1)

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
For more information see the terms of use .
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 17497689 Submission Date: 17 Nov 2010 08:31:45 UTC Last Modification Date: 29 Nov 2011 11:56:05 UTC Creation Date: 17 Nov 2010 08:39:05 UTC
Mathematical expressions
Reactions
RA_synthesis RA_decay RA_deg_by_Cyp26 M_C_transcription
M_C_decay C_translation C_decay FGF_synthesis
FGF_decay      
Rules
Assignment Rule (variable: FGF_mRNA) Assignment Rule (variable: vs1) Assignment Rule (variable: rho) Assignment Rule (variable: alpha2)
Assignment Rule (variable: alpha1)      
Physical entities
Compartments Species
PSM RA cyp26_mRNA CYP26
FGF FGF_mRNA  
Global parameters
vs1 kd5 kd1 V0
Vsc n Ka kd3
ks2 kd2 ks3 Ki
m kd4 ks1 RALDH2_0
x L M_0 rho
alpha2 alpha1 Kr1 Kr2
Reactions (9)
 
 RA_synthesis  → [RA];  
 
 RA_decay [RA] → ;  
 
 RA_deg_by_Cyp26 [RA] → ;   {CYP26}
 
 M_C_transcription  → [cyp26_mRNA];   {FGF}
 
 M_C_decay [cyp26_mRNA] → ;  
 
 C_translation  → [CYP26];   {cyp26_mRNA}
 
 C_decay [CYP26] → ;  
 
 FGF_synthesis  → [FGF];   {RA} , {FGF_mRNA}
 
 FGF_decay [FGF] → ;  
 
Rules (5)
 
 Assignment Rule (name: M_F) FGF_mRNA = M_0*x/L
 
 Assignment Rule (name: vs1) vs1 = ks1*RALDH2_0*(1-x/L)
 
 Assignment Rule (name: rho) rho = alpha2/alpha1
 
 Assignment Rule (name: alpha2) alpha2 = F/(F+Kr2)
 
 Assignment Rule (name: alpha1) alpha1 = RA/(RA+Kr1)
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 RA
Compartment: PSM
Initial concentration: 0.1
 
 cyp26_mRNA
Compartment: PSM
Initial concentration: 0.1
 
 CYP26
Compartment: PSM
Initial concentration: 0.1
 
 FGF
Compartment: PSM
Initial concentration: 1.0
 
  FGF_mRNA
Compartment: PSM
 
Global Parameters (24)
 
  vs1
Value: NaN   (Units: nM per min)
 
 kd5
Constant
 
 kd1
Value: 1.0   (Units: per nM per min)
Constant
 
 V0
Value: 0.365   (Units: nM per min)
Constant
 
 Vsc
Value: 7.1   (Units: nM per min)
Constant
 
 n
Value: 2.0   (Units: dimensionless)
Constant
 
 Ka
Value: 0.2   (Units: nM)
Constant
 
 kd3
Value: 1.0   (Units: per min)
Constant
 
 ks2
Value: 1.0   (Units: per min)
Constant
 
 kd2
Value: 0.28   (Units: per min)
Constant
 
 ks3
Value: 1.0   (Units: per min)
Constant
 
 Ki
Value: 0.2   (Units: nM)
Constant
 
 m
Value: 2.0   (Units: dimensionless)
Constant
 
 kd4
Value: 1.0   (Units: per min)
Constant
 
 ks1
Value: 1.0   (Units: per min)
Constant
 
 RALDH2_0
Value: 7.1   (Units: nM)
Constant
 
 x
Value: 15.0   (Units: arbit. length)
Constant
 
 L
Value: 50.0   (Units: arbit. length)
Constant
 
 M_0
Value: 5.0   (Units: nM)
Constant
 
  rho
Value: NaN   (Units: dimensionless)
 
  alpha2
Value: NaN   (Units: dimensionless)
 
  alpha1
Value: NaN   (Units: dimensionless)
 
 Kr1
Value: 1.0   (Units: nM)
Constant
 
 Kr2
Value: 1.0   (Units: nM)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000275

Curator's comment: (updated: 17 Nov 2010 08:38:28 GMT)

Recalculation of the results of figure 3 in the original publication. The calculations were performed using COPASI.
To create the plots parameter scans over the following initial conditions were performed:
Ka or Ki: 80 intervals from 0 to 0.6
FGF: 10 intervals from 0 to 100
RA: 5 intervals from 0 to 1

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