The Francis Crick Institute
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Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks.

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journal contribution
posted on 2021-03-31, 11:08 authored by Katherine Exelby, Edgar Herrera-Delgado, Lorena Garcia Perez, Ruben Perez-Carrasco, Andreas Sagner, Vicki Metzis, Peter Sollich, James Briscoe
During development, gene regulatory networks allocate cell fates by partitioning tissues into spatially organised domains of gene expression. How the sharp boundaries that delineate these gene expression patterns arise, despite the stochasticity associated with gene regulation, is poorly understood. We show, in the vertebrate neural tube, using perturbations of coding and regulatory regions, that the structure of the regulatory network contributes to boundary precision. This is achieved, not by reducing noise in individual genes, but by the configuration of the network modulating the ability of stochastic fluctuations to initiate gene expression changes. We use a computational screen to identify network properties that influence boundary precision, revealing two dynamical mechanisms by which small gene circuits attenuate the effect of noise in order to increase patterning precision. These results highlight design principles of gene regulatory networks that produce precise patterns of gene expression.


Crick (Grant ID: 10051, Grant title: Briscoe FC001051) Wellcome Trust (Grant ID: 098326/B/12/Z, Grant title: WT 098326/B/12/Z) European Research Council (Grant ID: 742138 - LogNeuroDev, Grant title: ERC 742138 - LogNeuroDev)