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由基因调控网络实现的时空模式形成

Spatiotemporal Patterning Enabled by Gene Regulatory Networks.

作者信息

Roy Ushasi, Singh Divyoj, Vincent Navin, Haritas Chinmay K, Jolly Mohit Kumar

机构信息

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore560012, India.

Undergraduate Programme, Indian Institute of Science, Bangalore560012, India.

出版信息

ACS Omega. 2023 Jan 17;8(4):3713-3725. doi: 10.1021/acsomega.2c04581. eCollection 2023 Jan 31.

Abstract

Spatiotemporal pattern formation plays a key role in various biological phenomena including embryogenesis and neural network formation. Though the reaction-diffusion systems enabling pattern formation have been studied phenomenologically, the biomolecular mechanisms behind these processes have not been modeled in detail. Here, we study the emergence of spatiotemporal patterns due to simple, synthetic and commonly observed two- and three-node gene regulatory network motifs coupled with their molecular diffusion in one- and two-dimensional space. We investigate the patterns formed due to the coupling of inherent multistable and oscillatory behavior of the toggle switch, toggle switch with double self-activation, toggle triad, and repressilator with the effect of spatial diffusion of these molecules. We probe multiple parameter regimes corresponding to different regions of stability (monostable, multistable, oscillatory) and assess the impact of varying diffusion coefficients. This analysis offers valuable insights into the design principles of pattern formation facilitated by these network motifs, and it suggests the mechanistic underpinnings of biological pattern formation.

摘要

时空模式形成在包括胚胎发育和神经网络形成在内的各种生物现象中起着关键作用。尽管能够形成模式的反应扩散系统已从现象学角度进行了研究,但这些过程背后的生物分子机制尚未得到详细建模。在此,我们研究了由于简单、合成且常见的两节点和三节点基因调控网络基序及其在一维和二维空间中的分子扩散而导致的时空模式的出现。我们研究了由于拨动开关、具有双重自激活的拨动开关、拨动三联体以及抑制器的固有多稳态和振荡行为与这些分子的空间扩散效应耦合而形成的模式。我们探究了对应于不同稳定性区域(单稳态、多稳态、振荡态)的多个参数范围,并评估了扩散系数变化的影响。该分析为这些网络基序促进模式形成的设计原则提供了有价值的见解,并揭示了生物模式形成的机制基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad95/9893257/9b05a3b4d016/ao2c04581_0001.jpg

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