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