Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks

TY - JOUR

T1 - Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks

AU - Exelby, Katherine

AU - Herrera-Delgado, Edgar

AU - Perez, Lorena Garcia

AU - Perez-Carrasco, Ruben

AU - Sagner, Andreas

AU - Metzis, Vicki

AU - Sollich, Peter

AU - Briscoe, James

N1 - Funding Information: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001051), the UK Medical Research Council (FC001051), and the Wellcome Trust (FC001051); the Wellcome Trust (WT098325MA and WT098326MA); and the European Research Council (under the European Union Horizon 2020 research and innovation program grant 742138). R.P.-C. acknowledges the University College London Mathematics Clifford Fellowship. Deposited in PMC for immediate release. Publisher Copyright: © 2021. Published by The Company of Biologists Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/25

Y1 - 2021/2/25

N2 - 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.

AB - 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.

KW - cis regulatory elements

KW - Dynamical systems theory

KW - Gene regulatory network

KW - Morphogen signaling

KW - Neural tube

UR - http://www.scopus.com/inward/record.url?scp=85102394362&partnerID=8YFLogxK

U2 - 10.1242/dev.197566

DO - 10.1242/dev.197566

M3 - Article

C2 - 33547135

AN - SCOPUS:85102394362

SN - 0950-1991

VL - 148

JO - Development (Cambridge, England)

JF - Development (Cambridge, England)

IS - 4

M1 - dev197566

ER -