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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 1 Xenopus life cycle MBT Wolpert et al. Principles of Development movie by Huw Williams 2 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 3 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 4 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 5 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 6 Gene network • positive feedback between two genes • A activates B • B activates A indirectly: • extra cellular pathway • mediated by diffusable D molecule 7 Positive feedback in cell community D diffuses between all cells 8 Modeling • We applied several approaches, with agreeing results • stochastic simulation (Gillespie algorithm) ✓ pi-calculus ✓ direct implementation in C • ordinary differential equations 9 Threshold in stochastic simulation 10 Deterministic model Allows analytical derivation of critical number nc from the steady state solution of the rate equations: 11 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 12 Thank you! Questions? Funding: Agence Nationale de Recherche CNRS Univ Lille 1 Scottish Life Science Alliances MMSRC 13 Davidson’s gene network confirms ours sea urchin embryo [Davidson & Bolouri 2010] • similar topology for community effect occurs in many organisms! 14 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] 15