The community effect in animal development - coordinated gene expression in a group of cells

Cline Kuttler & Lhoussaine (Lille University) Y. Saka, Thiel & Ullner (Aberdeen University)

To appear in BMC Systems Biology

Xenopus life cycle

MBT

Wolpert et al. Principles of Development

movie by Huw Williams

A community effect in animal development

(Gurdon, 1988)

interaction among a group of nearby cells in a

developing embryo.

initially , an external signal establishes the group coordinated gene expression is

molecule

maintained only if group size exceeds critical number nc .

communication between cellsthrough a diffusible

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Where else does community effect, or similar communication, occur?

development of many other tumor development quorum sensing in

bacteria

organisms [Davidson et al]

sea urchin embryo

Gurdons experiments on community effect in Xenopus embryo (1993)

nc

individual cells: never

activated only cells in groups can be

Gurdon et al., 1993

activated threshold group size ~ 100

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Questions addressed in this work

1. Whats the minimal gene network

required for self-sustaining gene expression?

structure of model
2. How to control the community sizes
threshold?

quantitative tuning of model

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Gene network
positive feedback between
two genes

A activates B B activates A indirectly: extra cellular pathway mediated by

diffusable D molecule
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Positive feedback in cell community

D diffuses between all cells

Modeling

We applied several approaches, with

agreeing results algorithm)

stochastic simulation (Gillespie ordinary differential equations

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pi-calculus direct implementation in C

Threshold in stochastic simulation

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Deterministic model
Allows analytical derivation of critical number nc from the steady state solution of the rate equations:

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Conclusion and future work

We provided a minimal gene network for
self-sustaining gene expression, that

exhibits the community effect, and conrms and renes Davidsons work. Future work: controlling the community effect in space

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Thank you! Questions?

Funding: Agence Nationale de Recherche CNRS Univ Lille 1 Scottish Life Science Alliances MMSRC
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Davidsons gene network conrms ours

sea urchin embryo

[Davidson & Bolouri 2010]

similar topology for community effect occurs in many organisms!

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Davidsons question: why does activation saturate below 100%?

negative feedback in sea urchin: lefty is activated by a signal, and
eventually turns off this same signal [Davidson & Bolouri 2010]

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