MODEL SEGMENTATION CLOCK NETWORK PARAMETERS ... - PLOS

MODEL SEGMENTATION CLOCK NETWORK PARAMETERS AND INITIAL CONDITIONS Parameters: Notch loop Parameter Description vsN Maximum rate of Notch synthesis vdN Maximum rate of Notch degradation KdN Michaelis constant for Notch degradation kc Rate constant for Notch cleavage vdNa Maximum rate of cytoplasmic NICD degradation KdNa Michaelis constant for cytoplasmic NICD degradation vdNan Maximum rate of nuclear NICD degradation KdNan Michaelis constant for nuclear NICD degradation KIF Threshold constant for inhibition of Notch cleavage by Lfng KaDL Delta signaling threshold constant for Notch cleavage kt1 Rate constant for NICD entry into nucleus kt2 Rate constant for NICD exit from the nucleus vNap Maximum fraction of NICD phosphorylated KpN Threshold constant for Gsk3β-mediated NICD phosphorylation vsF Maximum rate of Lfng transcription KA Threshold constant for activation of Lfng gene by NICD vmF Maximum rate of Lfng mRNA degradation KdmF Michaelis constant for Lfng mRNA degradation ksF Rate constant for Lfng protein synthesis vdF Maximum rate of Lfng protein degradation KdF Michaelis constant for Lfng protein degradation vs0MDMF Maximum rate of DMF transcription KaNDMF Michaelis constant for Notch activation of DMF vdmDMF Maximum rate of DMF mRNA degradation KdmDMF Michaelis constant for DMF mRNA degradation KsDMF Rate constant for translation of DMF vdDMF Maximum rate of DMF protein degradation KdDMF Michaelis constant for DMF protein degradation ksDL Rate constant for Delta protein synthesis MDL Concentration of Delta mRNA KNan Michaelis constant for NICD stimulation of Delta translation ktDL Rate constant for Delta protein transport to membrane vdDLc Maximum rate of Delta protein degradation in cytoplasm KdDLc Michaelis constant for Delta protein degradation in cytoplasm vdDLm Maximum rate of Delta protein degradation on membrane KdDLm Michaelis constant for Delta protein degradation on membrane KDL Threshold constant for Delta signaling ε Scaling factor for Notch loop Parameters in bold are additions to the Goldbeter-Pourquié model.

Value 0.23 nM/min 2.82 nM/min 1.4 nM 3.45 min-1 0.01 nM/min 0.001 nM 0.1 nM/min 0.001 nM 0.45 nM 0.035 nM 0.1 min-1 0.1 min-1 1.0 2.5 nM 3.24 nM/min 0.05 nM 1.92 nM/min 0.768 nM 0.3 min-1 0.39 nM/min 0.37 nM 0.497 nM/min 0.05 nM 0.314 nM/min 0.4 nM 0.1047 min-1 0.209 nM/min 0.5 nM 0.75 min-1 0.5 nM 0.04 nM 0.5 min-1 0.5 nM/min 0.5 nM 0.5 nM/min 0.5 nM 0.08 nM 0.43

Wnt loop Parameter a1 d1 vsB kt3 kt4 VMK Kt KID K1 VMP K2 kd1 kd2 v0 vMB KaB vmd Kmd vMXa KaXa KsAx vdAx KdAx θ

Description Rate constant for Gsk3β-Axin2 binding Rate constant for Gsk3β-Axin2 dissociation Maximum rate of β-catenin synthesis Rate constant for β-catenin entry into the nucleus Rate constant for β-catenin exit from the nucleus Maximum rate of Gsk3β-mediated β-catenin phosphorylation Total Gsk3β concentration Threshold constant for Dsh inhibition of β-catenin phosphorylation Michaelis constant for β-catenin phosphorylation Maximum rate of β-catenin dephosphorylation Michaelis constant for β-catenin dephosphorylation Rate constant for unphosphorylated β-catenin degradation Rate constant for phosphorylated β-catenin degradation Basal rate of Axin2 transcription Maximum rate of β-catenin activated Axin2 transcription Threshold constant for β-catenin activation of Axin2 Maximum rate of Axin2 mRNA degradation Michaelis constant for Axin2 mRNA degradation Maximum rate of Xa activated Axin2 transcription Threshold constant for Xa activation of Axin2 Rate constant for Axin2 translation Maximum rate of Axin2 protein degradation Michaelis constant for Axin2 protein degradation Scaling factor for Wnt loop

Value 1.8 nM-1 min-1 0.1 min-1 0.087 nM/min 0.7 min-1 -1 1.5 min 4.5 nM/min 3.0 nM 0.5 nM 0.28 nM 1.0 nM/min 0.03 nM 0.0 min-1 7.062 min-1 0.06 nM/min 1.64 nM/min 0.7 nM 0.8 nM/min 0.48 nM 0.5 nM/min 0.05 nM 0.02 min-1 0.6 nM/min 0.63 nM 1.12

Description Total concentration of Ras protein Maximum rate of Ras activation FGF8 threshold constant for activation of Ras Inactive Ras threshold constant for activation of Ras Maximum rate of Ras activation Michaelis constant for Ras inactivation Total concentration of ERK protein kinase Maximum rate of Ras-mediated ERK activation Inactive ERK threshold constant for ERK activation Rate constant for inactivation of ERK Michaelis constant for inactivation of ERK Total concentration of factor X Maximum rate of ERK-mediated X activation Threshold constant for ERK-mediated X activation Maximum rate of X inactivation Michaelis constant for X inactivation Maximum rate of Dusp6 transcription Threshold constant for X-activated Dusp6 transcription Maximum rate of Dusp6 mRNA degradation Michaelis constant for Dusp6 mRNA degradation Rate constant for Dusp6 translation

Value 2.0 nM 4.968 nM/min 0.5 nM 0.103 nM 0.41 nM/min 0.1 nM 2.0 nM 3.3 nM/min 0.05 nM 1.35 min-1 0.05 nM 2.0 nM 1.6 nM/min 0.05 nM 0.5 nM/min 0.05 nM 0.9 nM/min 0.5 nM 0.5 nM/min 0.5 nM 0.5 min-1

FGF loop Parameter Rast VMaRas KaFgf KaRas VMdRas KdRas ERKt VMaErk KaErk KcDusp KdErk Xt VMaX KaX VMdX KdX VMsMDusp KaMDusp VMdMDusp KdMDusp ksDusp

VdDusp Maximum rate of Dusp6 protein degradation KdDusp Michaelis constant for Dusp6 protein degradation vDuspX Fraction of Dusp6 transcription solely regulated by X vDuspDMF Fraction of Dusp6 transcription under regulation by DMF KIMDusp Threshold constant for DMF-mediated inhibition of Dusp6 ν Scaling factor for FGF8 loop Parameters in bold are additions to the Goldbeter-Pourquié model.

2.0 nM/min 0.5 nM 0.2 0.8 0.3 nM 0.328

Initial variable values: Notch loop Variable Description N Notch in the membrane Na Activated Notch Nan Activated Notch in the nucleus Nap Phosphorylated Notch MF Lunatic Fringe mRNA F Lunatic Fringe protein MDMF Delta Modification Factor mRNA DMF Delta Modification Factor protein DLc Delta protein in the cytoplasm DLm Delta protein on the membrane Variables in bold are additions to the Goldbeter-Pourquié model.

Value

0.0552 nM 0.8095 nM 0.0039 nM 0.0013 nM 0.003 nM 0.0006 nM 0.0011 nM 0.0003 nM 0.0138 nM 0.0058 nM

Wnt loop Variable K B Bp BN Max A AK

Description Free Gsk3 protein β-catenin Phosphorylated β-catenin Nuclear β-catenin Axin2 mRNA Axin2 protein Axin2-Gsk3 complex

Value

Description Activated Ras protein Activated ERK protein Activated transcription factor X Dusp mRNA Dusp protein

Value

1.2252 nM 0.9118 nM 0.0171 nM 0.4324 nM 7.7560 nM 0.1076 nM 1.7747 nM

FGF loop Variable Rasa ERKa Xa MDusp Dusp

1.9912 nM 1.9780 nM 1.9777 nM 2.9054 nM 0.7692 nM