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Martin Howard (John Innes Centre, Norwich)

Modelling noisy concentration gradients in developmental biology



Many biological systems require precise positional information to function correctly. A prominent example is the determination of cell fate during embryonic development. This positional information is often encoded in concentration gradients of morphogen proteins. By switching on a signal only where the local concentration is above a certain threshold, this gradient can provide positional information. However, intrinsic randomness in biochemical reactions and diffusion, as well as external embryo-to-embryo fluctuations, will lead to unavoidable variation in the concentration profile, which in turn will lead to fluctuations in the identified position. We therefore investigated how precisely a noisy concentration gradient can specify positional information. We found that both the kinetic parameters and the overall functional form of a concentration gradient can be optimised to generate maximally precise positional information. We have also analysed fluctuation in gradients that have not reached steady-state. Here we conclude that pre-steady-state read out of morphogen gradients does not generally lead to more precise positional information, contrary to earlier claims.