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Spatial information: several germ layer specific Pou5f1 targets are transcriptional repressors:
Pou5f1 no Pou5f1
foxD3
Sox-independent
her3
Sox-dependent
klf2b
Sox-dependentPou5f1 no Pou5f1
Pou5f1Pou5f1
Pou5f1 no Pou5f1
promote differentiation
(POD)
Decision making in time
time
statereversible decision making
spatial information input
Pou5f1
promote decision
repress decison
open state
-pluri-
potent
sharpen-ing
decisionfixed final states
Sox act with Pou5f1
repress decisonrepress
differentiation (ROD)
3
Temporal dynamics of Pou5f1 target network
Temporal behaviour of Sox, RODs and PODSimulation versus measurements
with Pou5f1without Pou5f1
“half” amount of Pou5f1prediction“half” amount of Pou5f1measurements
differentiation genes prematurely activated in absence of Pou5f1
Pou5f1 targets:early “monophasic”activation(ROD)
Pou5f1 + Sox targets:delayed “biphasic”activation(ROD)
Explanation for the Dual Role of Pou5f1
The dual role of Pou5f1 in activating promotors of differentiation (PoDs) and also repressing them indirectly by RODs allows to control the time of differentiation
Decision making in time
time
statereversible decision making
spatial information input
Pou5f1
promote decision
repress decison
open state
-pluri-
potent
sharpen-ing
decisionfixed final states
Sox acts with Pou5f1
repress PODs
promote decision
repress decisonrepress PODs FoxD3 ROD Type I
Her3 ROD Type II
Decision making in time I: early Pou5f1 and late Pou5f1/Sox dependent
activation
time
statereversible decision making
spatial information input
Pou5f1
promote decision
open state
-pluri-
potent
sharpen-ing
decisionfixed final states
Sox acts with Pou5f1
promote decision
Decision making in time II: balance of repression and activation times developmental progress
time
statereversible decision making
spatial information input
Pou5f1
promote decision
repress decison
open state
-pluri-
potent
sharpen-ing
decisionfixed final states
Sox acts with Pou5f1
repress PODs
promote decision
repress decisonrepress PODs FoxD3 ROD Type I
Her3 ROD Type II