Download The community effect in animal development

The community effect in animal development
- coordinated gene expression in a group of cells
Céline Kuttler & Lhoussaine (Lille University)
Y. Saka, Thiel & Ullner (Aberdeen University)
To appear in BMC
Systems Biology
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Xenopus life cycle
MBT
Wolpert et al. Principles of Development
movie by Huw Williams
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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
maintained only if group size exceeds critical
number nc .
• communication between cellsthrough a diffusible
molecule
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Where else does community
effect, or similar communication,
occur?
• development of many other
organisms [Davidson et al]
sea urchin embryo
• tumor development
• quorum sensing in
bacteria
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Gurdon’s 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. What’s the minimal gene network
required for self-sustaining gene expression?
• structure of model
2. How to control the community size’s
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
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Modeling
• We applied several approaches, with
agreeing results
• stochastic simulation (Gillespie
algorithm)
✓ pi-calculus
✓ direct implementation in C
• ordinary differential equations
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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
• confirms and refines Davidson’s 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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Davidson’s gene network
confirms ours
sea urchin embryo
[Davidson & Bolouri 2010]
•
similar topology for community effect occurs in many organisms!
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Davidson’s 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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