658668
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Complex Wnt-Frzzl
type: Species

659118
constant: true
value: 1.0
type: Parameter

658651
is version of: P18537
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Frzzl
type: Species

659130
constant: true
value: 1.0
type: Parameter

658828
kinetic law: 247415
product: 247403
reactant: 247391
reactant: 247379
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true
type: Reaction

658345
is version of: P46531
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: NICD
type: Species

247438
stoichiometry: 1.0
species: 658464
type: SpeciesReference

658481
is version of: Q15465
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Shh
type: Species

659139
constant: true
value: 1.0
type: Parameter

659088
constant: true
value: 1.0
type: Parameter

BIOMD0000000398
parameter: 659133
reaction: 658991
parameter: 659106
reaction: 658928
species: 658737
species: 658583
is: MODEL1111020000
time units: 949038
reaction: 658969
parameter: 659064
reaction: 659010
species: 658431
parameter: 659076
species: 658481
species: 658515
species: 658363
parameter: 659115
reaction: 659030
parameter: 659088
substance units: 142808
parameter: 659067
parameter: 659154
reaction: 658828
curated: true
parameter: 659127
species: 658345
parameter: 659160
parameter: 659166
reaction: 658886
parameter: 659139
parameter: 659112
parameter: 659118
species: 658617
parameter: 659172
parameter: 659145
parameter: 659151
name: Sivakumar2011_NeuralStemCellDifferentiation_Crosstalk
parameter: 659124
species: 658787
parameter: 659163
compartment: 658329
parameter: 659136
is described by: http://identifiers.org/pubmed/21978399
parameter: 659148
species: 658533
is version of: GO:0007173
is version of: GO:0060070
species: 658447
is version of: GO:0007219
type: SBMLModel
species: 658600
parameter: 659079
species: 658668
species: 658651
reaction: 658849
parameter: 659073
parameter: 659157
species: 658702
species: 658549
parameter: 659085
parameter: 659169
reaction: 658867
notes: This model is from the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. OMICS 2011 Oct;15(10):729-37. 21978399 , Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to in fluence cell fate specification in the developing nervous system. Here we attempt ed to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Ou r model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E (spl)] genes and enhancement of Shh target genes by a SAG agonist that were effec tively demonstrated computationally and were consistent with experimental studies . However, in the case of model simulation of Wnt and EGF pathways, the model net work did not supply any concurrent results with experimental data despite the fac t that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species conne cted by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted th e regulation of a single target gene, Hes-1, based on drug-induced simulations. T hese simulations provided results that matched with experimental studies. Therefo re, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferati on, and differentiation during mammalian central nervous system development. To o ur knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores t he flow of positive and negative regulatory signals modulated by drugs.
reaction: 658948
species: 658770
parameter: 659100
parameter: 659097
reaction: 658806
species: 658719
compartment: 658326
parameter: 659082
parameter: 659094
species: 658498
species: 658380
species: 658464
species: 658414
area units: 498119
volume units: 142784
species: 658396
length unit: length

247654
stoichiometry: 1.0
species: 658686
type: SpeciesReference

659073
constant: true
value: 1.0
type: Parameter

659079
constant: true
value: 1.0
type: Parameter

658464
is: http://identifiers.org/omim/139605
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658329
name: Hes-1
type: Species

659103
constant: true
value: 1.0
type: Parameter

658396
is version of: GO:0070765
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Gamma secretase
type: Species

247582
stoichiometry: 1.0
species: 658464
type: SpeciesReference

659148
constant: true
value: 1.0
type: Parameter

247822
stoichiometry: 1.0
species: 658533
type: SpeciesReference

247522
stoichiometry: 1.0
species: 658583
type: SpeciesReference

659082
constant: true
value: 1.0
type: Parameter

659160
constant: true
value: 1.0
type: Parameter

659169
constant: true
value: 1.0
type: Parameter

658770
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Complex GSK3B-Bcatenin
type: Species

247726
stoichiometry: 1.0
species: 658753
type: SpeciesReference

247403
stoichiometry: 1.0
species: 658447
type: SpeciesReference

658380
is version of: CHEBI:36080
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Notch TM
type: Species

658686
is homolog to: Q86TH3
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Dishevelled
type: Species

659142
constant: true
value: 1.0
type: Parameter

659091
constant: true
value: 1.0
type: Parameter

247666
stoichiometry: 1.0
species: 658702
type: SpeciesReference

659085
constant: true
value: 1.0
type: Parameter

658991
kinetic law: 247810
product: 247798
reactant: 247786
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true
type: Reaction

658600
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Complex EGF-EGFR
type: Species

247882
stoichiometry: 1.0
species: 658533
type: SpeciesReference

659109
constant: true
value: 1.0
type: Parameter

658948
reversible: true
type: Reaction
reactant: 247654
product: 247678
reactant: 247666
modifier: 247690
fast: false
notes: reversible rapid-equilibrium random order ternary-complex mechanism with one product
kinetic law: 247702

659121
constant: true
value: 1.0
type: Parameter

658753
is homolog to: Q02248
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Beta-catenin
type: Species

247630
stoichiometry: 1.0
species: 658668
type: SpeciesReference

658719
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Complex Dishevelled-FRAT-CK2
type: Species

659067
constant: true
value: 1.0
type: Parameter

659136
constant: true
value: 1.0
type: Parameter

658908
kinetic law: 247594
product: 247582
reactant: 247570
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true
type: Reaction

658886
kinetic law: 247558
type: Reaction
product: 247534
reactant: 247510
fast: false
reactant: 247522
reversible: true
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
modifier: 247546

247462
stoichiometry: 1.0
species: 658481
type: SpeciesReference

247738
stoichiometry: 1.0
species: 658770
type: SpeciesReference

247618
stoichiometry: 1.0
species: 658651
type: SpeciesReference

659070
constant: true
value: 1.0
type: Parameter

659157
constant: true
value: 1.0
type: Parameter

247534
stoichiometry: 1.0
species: 658600
type: SpeciesReference

659100
constant: true
value: 1.0
type: Parameter

658549
is version of: P10523
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: SAG
type: Species

658928
kinetic law: 247642
product: 247630
reactant: 247618
reactant: 247606
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true
type: Reaction

247510
stoichiometry: 1.0
species: 658567
type: SpeciesReference

658635
is version of: P56704
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Wnt
type: Species

658329
constant: true
size: 1.0
spatial dimensions: 3.0
name: nucleus
type: Compartment

247894
stoichiometry: 1.0
species: 658464
type: SpeciesReference

247319
stoichiometry: 1.0
species: 658345
type: SpeciesReference

247486
stoichiometry: 1.0
species: 658515
type: SpeciesReference

658515
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Complex Shh Ptch1
type: Species

659064
constant: true
value: 1.0
type: Parameter

247678
stoichiometry: 1.0
species: 658719
type: SpeciesReference

659097
constant: true
value: 1.0
type: Parameter

658849
kinetic law: 247450
product: 247438
reactant: 247426
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true
type: Reaction

659145
constant: true
value: 1.0
type: Parameter

247606
stoichiometry: 1.0
species: 658635
type: SpeciesReference

247798
stoichiometry: 1.0
species: 658464
type: SpeciesReference

247834
stoichiometry: 1.0
species: 658533
type: SpeciesReference

659115
constant: true
value: 1.0
type: Parameter

659163
constant: true
value: 1.0
type: Parameter

658702
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: FRAT-CK2
type: Species

247331
stoichiometry: 1.0
species: 658380
type: SpeciesReference

247391
stoichiometry: 1.0
species: 658431
type: SpeciesReference

658737
is version of: P49841
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: GSK3B
type: Species

658969
kinetic law: 247774
modifier: 247762
reversible: true
reactant: 247726
fast: false
product: 247738
reactant: 247714
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
modifier: 247750
type: Reaction

658533
is version of: Q99835
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: smo
type: Species

659124
constant: true
value: 1.0
type: Parameter

658617
is version of: CHEBI:114785
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 100.0
in compartment: 658326
name: Erlotinib
type: Species

659154
constant: true
value: 1.0
type: Parameter

658567
is version of: P01133
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: EGF
type: Species

658414
is version of: CHEBI:36080
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 100.0
in compartment: 658326
name: DAPT
type: Species

658447
is version of: GO:0043234
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 0.0
in compartment: 658326
name: Complex NICD-RBP
type: Species

659106
constant: true
value: 1.0
type: Parameter

659133
constant: true
value: 1.0
type: Parameter

247307
stoichiometry: 1.0
species: 658363
type: SpeciesReference

247379
stoichiometry: 1.0
species: 658345
type: SpeciesReference

247474
stoichiometry: 1.0
species: 658498
type: SpeciesReference

659076
constant: true
value: 1.0
type: Parameter

659010
notes: kinetics of non-modulated unireactant enzymes
type: Reaction
kinetic law: 247870
reversible: true
modifier: 247846
product: 247834
fast: false
reactant: 247822
modifier: 247858

658498
is homolog to: Q13635
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Ptch1
type: Species

658806
reactant: 247307
reversible: true
type: Reaction
modifier: 247343
kinetic law: 247367
product: 247331
fast: false
product: 247319
modifier: 247355
notes: reversible thermodynamically independent convenience kinetics

658867
kinetic law: 247498
product: 247486
reactant: 247474
reactant: 247462
notes: mass action rate law for second order forward, first order reverse, reversible reactions, two reactants, continuous scheme
fast: false
reversible: true
type: Reaction

659151
constant: true
value: 1.0
type: Parameter

659127
constant: true
value: 1.0
type: Parameter

247786
stoichiometry: 1.0
species: 658753
type: SpeciesReference

658431
is version of: Q06330
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: RBP-jk
type: Species

659030
kinetic law: 247918
modifier: 247906
product: 247894
reactant: 247882
notes: mass action rate law for first order forward, first order reverse, reversible reactions, continuous scheme
fast: false
reversible: true
type: Reaction

247714
stoichiometry: 1.0
species: 658737
type: SpeciesReference

658363
is homolog to: P07207
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: Notch
type: Species

659094
constant: true
value: 1.0
type: Parameter

658326
constant: true
size: 1.0
spatial dimensions: 3.0
type: Compartment

659172
constant: true
value: 1.0
type: Parameter

658583
is version of: Q147T7
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 5.0
in compartment: 658326
name: EGFR
type: Species

247426
stoichiometry: 1.0
species: 658447
type: SpeciesReference

658787
is version of: CHEBI:25750
constant: false
boundary condition: false
has only substance units: false
initial concentration: NaN
initial amount: 100.0
in compartment: 658326
name: 6 bromoindirubin 3`oxime
type: Species

659112
constant: true
value: 1.0
type: Parameter

247570
stoichiometry: 1.0
species: 658600
type: SpeciesReference

659166
constant: true
value: 1.0
type: Parameter

ORG:
  orgname: Rajiv Gandhi Centre for Biotechnology
n:
  given: KC
  family: Sivakumar

orgname: EMBL-EBI

given: Vijayalakshmi
family: Chelliah

W3 CDTF: Fri Apr 20 20:38:05 BST 2012

W3 CDTF: Wed Nov 02 14:54:21 GMT 2011