Developmental Dynamics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Developmental Dynamics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Development. 2021 Feb 25;148(4):dev197566. doi: 10.1242/dev.197566.
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.
在发育过程中,基因调控网络通过将组织分配到基因表达的空间组织区域来分配细胞命运。尽管与基因调控相关的随机性很大,但仍然不清楚如何形成这些基因表达模式的鲜明边界。我们使用编码和调节区域的扰动,在脊椎动物神经管中表明,调节网络的结构有助于边界精度。这不是通过降低单个基因的噪声来实现的,而是通过网络的配置来调节随机波动引发基因表达变化的能力来实现的。我们使用计算筛选来识别影响边界精度的网络特性,揭示了两个小基因电路衰减噪声影响以提高模式化精度的动态机制。这些结果突出了基因调控网络的设计原则,这些原则产生了精确的基因表达模式。