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

• Published in: Developmental biology Vol. 518; pp. 85 - 97
• Main Authors: Cano-Fernández, Hugo, Tissot, Tazzio, Brun-Usan, Miguel, Salazar-Ciudad, Isaac
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2025
• Subjects: adhesion; Animals; bioinformatics; Cell division; Cell Division - genetics; Computer Simulation; epithelium; Epithelium - metabolism; Evolution; Gene Expression Regulation, Developmental - genetics; Gene networks; Gene Regulatory Networks; genes; Long-range signaling; mathematical models; Models, Biological; Morphogenesis; Noise; Robustness; Signal Transduction - genetics; Morphogenesis; Gene networks; Noise; Long-range signaling; Cell division; Evolution; Robustness
• ISSN: 0012-1606; 1095-564X; 1095-564X
• DOI: 10.1016/j.ydbio.2024.11.014

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. [Display omitted] •We used the model EmbryoMaker to study the sources of cell-level developmental noise.•Cell division creates random folds because it is an anisotropic process.•Random folds are reduced by rigid epithelia, slow division rate and controlled folds.•Self-activation loops of non-diffusive molecules maintain noise.•Short-range signaling increases noise, long-range signaling decreases noise.