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一个发育的数学模型表明,细胞分裂、短程信号传导和自我激活基因网络会增加发育噪声,而长程信号传导和上皮硬度则会降低发育噪声。

A mathematical model of development shows that cell division, short-range signaling and self-activating gene networks increase developmental noise while long-range signaling and epithelial stiffness reduce it.

作者信息

Cano-Fernández Hugo, Tissot Tazzio, Brun-Usan Miguel, Salazar-Ciudad Isaac

机构信息

Genomics, Bioinformatics and Evolution Group, Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Edifici C, 08193, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.

Electronics and Computer Science Department, University of Southampton, University Road, Southampton, SO17 1BJ, UK.

出版信息

Dev Biol. 2025 Feb;518:85-97. doi: 10.1016/j.ydbio.2024.11.014. Epub 2024 Nov 30.

Abstract

The position of cells during development is constantly subject to noise, i.e. cell-level noise. We do not yet fully understand how cell-level noise coming from processes such as cell division or movement leads to morphological noise, i.e. morphological differences between genetically identical individuals developing in the same environment. To address this question we constructed a large ensemble of random genetic networks regulating cell behaviors (contraction, adhesion, etc.) and cell signaling. We simulated them with a general computational model of development, EmbryoMaker. We identified and studied the dynamics, under cell-level noise, of those networks that lead to the development of animal-like morphologies from simple blastula-like initial conditions. We found that growth by cell division is a major contributor to morphological noise. Self-activating gene network loops also amplified cell-level noise into morphological noise while long-range signaling and epithelial stiffness tended to reduce morphological noise.

摘要

细胞在发育过程中的位置不断受到噪声影响,即细胞水平的噪声。我们尚未完全理解诸如细胞分裂或移动等过程产生的细胞水平噪声是如何导致形态噪声的,也就是在相同环境中发育的基因相同个体之间的形态差异。为了解决这个问题,我们构建了大量调节细胞行为(收缩、黏附等)和细胞信号传导的随机遗传网络。我们使用通用的发育计算模型“胚胎生成器”对它们进行模拟。我们识别并研究了在细胞水平噪声下,那些能从类似囊胚的简单初始条件发育出动物样形态的网络的动态变化。我们发现细胞分裂导致的生长是形态噪声的主要成因。自我激活基因网络回路也会将细胞水平噪声放大为形态噪声,而长距离信号传导和上皮组织硬度则倾向于降低形态噪声。

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