预印本 / 版本 1

A kinematic equation for the morphogenetic reproducibility of an animal

本文是预印本,尚未经过同行评审认证。

作者

    Jianguo Wang, 
    Jianguo Wang
    • Sun Yat-sen University image/svg+xml
    • Hongkong Institute for Advanced Studies, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
    Long Xiao, 
    Long Xiao
    • State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
    Miaoling Yang, 
    Miaoling Yang
    • State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
    Zeqi Yao, 
    Zeqi Yao
    • Hongkong Institute for Advanced Studies, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
    Shanjun Deng, 
    Shanjun Deng
    • Hongkong Institute for Advanced Studies, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
    Zhuo Du, 
    Zhuo Du
    • State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
    Xionglei He
    Xionglei He
    • Hongkong Institute for Advanced Studies, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
分类
关键词
morphogenesis; embryogenesis; developmental reproducibility; canalization; self-similarity; golden ratio

摘要

It is intriguing how cell positioning is regulated during animal development to achieve reproducible morphogenesis under genetic or environmental perturbations.  In this study, we track single-cell spatiotemporal dynamics in over 2,000 C. elegans embryos subjected to diverse perturbations.  By analyzing the inheritance of cell position along developmental lineages, we uncover ubiquitous negative-feedback “canals” that prevent the propagation of positional noise, thereby ensuring morphogenetic reproducibility.  Examining cell kinematic parameters reveals that cell migration velocity underlies the negative-feedback regulation.  The velocity dynamics across cell generations are described by a self-similar equation characterized by a single parameter φ (the golden ratio) that quantifies velocity adjustment, suggesting an inherent program recurrently employed by cells to attain their expected positions.  Further analysis shows that φ = 0.618 represents the theoretical optimum, enabling an expected zero net noise accumulation and thus along-lineage conservation of cell velocity.  Deviation from this self-similar equation predicts hatching failure (AUC = 0.89), and reveals a set of cytoskeleton-enriched genes required for its maintenance.  In summary, by revealing a conservation principle of cell kinematics in C. elegans embryos, this study establishes a novel kinematic-mechanical framework for investigating animal morphogenesis, highlighting a golden-ratio-embedded natural design adaptable to general dynamic systems for noise control.

参考文献

Zhu, M. & Zernicka-Goetz, M. Principles of Self-Organization of the Mammalian Embryo. Cell 183, 1467-1478 (2020).

Scharloo, W. Canalization: genetic and developmental aspects. Annual Review of Ecology and Systematics 22, 65-93 (1991).

Waddington, C. H. Canalization of development and the inheritance of acquired characteres. Nature 150, 563-565 (1942).

Osterwalder, M. et al. Enhancer redundancy provides phenotypic robustness in mammalian development. Nature 554, 239-243 (2018).

Karras, G. I. et al. HSP90 Shapes the Consequences of Human Genetic Variation. Cell 168, 856-866 e812 (2017).

Hornstein, E. & Shomron, N. Canalization of development by microRNAs. Nat Genet 38 Suppl, S20-24 (2006).

Siegal, M. L. & Bergman, A. Waddington's canalization revisited: developmental stability and evolution. Proc Natl Acad Sci U S A 99, 10528-10532 (2002).

Mao, Y. & Wickstrom, S. A. Mechanical state transitions in the regulation of tissue form and function. Nat Rev Mol Cell Biol 25, 654-670 (2024).

Mitchell, S. J., Pardo-Pastor, C., Tchoumakova, A., Zangle, T. A. & Rosenblatt, J. Energy deficiency selects crowded live epithelial cells for extrusion. Nature 646, 1187-1194 (2025).

Zhang, Y., Cohen, O. Y., Moshe, M. & Sharon, E. Geometrically frustrated rose petals. Science 388, 520-524 (2025).

Caldarelli, P. et al. Self-organized tissue mechanics underlie embryonic regulation. Nature 633, 887-894 (2024).

Fabreges, D. et al. Temporal variability and cell mechanics control robustness in mammalian embryogenesis. Science 386, eadh1145 (2024).

Firmin, J. et al. Mechanics of human embryo compaction. Nature 629, 646-651 (2024).

Nelson, C. M. et al. Mechanobiology: Shaping the future of cellular form and function. Cell 187, 2652-2656 (2024).

Naganathan, S. R., Popovic, M. & Oates, A. C. Left-right symmetry of zebrafish embryos requires somite surface tension. Nature 605, 516-521 (2022).

Guignard, L. et al. Contact area-dependent cell communication and the morphological invariance of ascidian embryogenesis. Science 369, 158-+ (2020).

Saadaoui, M., Rocancourt, D., Roussel, J., Corson, F. & Gros, J. A tensile ring drives tissue flows to shape the gastrulating amniote embryo. Science 367, 453-458 (2020).

Collinet, C. & Lecuit, T. Programmed and self-organized flow of information during morphogenesis. Nat Rev Mol Cell Biol 22, 245-265 (2021).

Negrete, J., Jr. & Oates, A. C. Towards a physical understanding of developmental patterning. Nat Rev Genet 22, 518-531 (2021).

Villeneuve, C., McCreery, K. P. & Wickstrom, S. A. Measuring and manipulating mechanical forces during development. Nature cell biology 27, 575-590 (2025).

Moghe, P. et al. Coupling of cell shape, matrix and tissue dynamics ensures embryonic patterning robustness. Nature cell biology 27, 408-423 (2025).

Ishihara, K. et al. Topological morphogenesis of neuroepithelial organoids. Nat Phys 19, 177-183 (2023).

Fernandez, P. A. et al. Surface-tension-induced budding drives alveologenesis in human mammary gland organoids. Nat Phys 17, 1130-1136 (2021).

Shen, J., Liu, F. & Tang, C. Scaling dictates the decoder structure. Sci Bull (Beijing) 67, 1486-1495 (2022).

Chan, C. J. et al. Hydraulic control of mammalian embryo size and cell fate. Nature 571, 112-116 (2019).

Gross, P. et al. Guiding self-organized pattern formation in cell polarity establishment. Nat Phys 15, 293-300 (2019).

Hannezo, E. et al. A Unifying Theory of Branching Morphogenesis. Cell 171, 242-255 e227 (2017).

Atia, L. et al. Geometric constraints during epithelial jamming. Nat Phys 14, 613-620 (2018).

Shah, G. et al. Multi-scale imaging and analysis identify pan-embryo cell dynamics of germlayer formation in zebrafish. Nat Commun 10, 5753 (2019).

Xue, S. L., Yang, Q., Liberali, P. & Hannezo, E. Mechanochemical bistability of intestinal organoids enables robust morphogenesis. Nat Phys 21, 608-617 (2025).

Hota, S. K. et al. Brahma safeguards canalization of cardiac mesoderm differentiation. Nature 602, 129-134 (2022).

Xiao, L., Fan, D., Qi, H., Cong, Y. & Du, Z. Defect-buffering cellular plasticity increases robustness of metazoan embryogenesis. Cell Syst 13, 615-630 e619 (2022).

Yang, Q. et al. Cell fate coordinates mechano-osmotic forces in intestinal crypt formation. Nature cell biology 23, 733-744 (2021).

Hoijman, E. et al. Cooperative epithelial phagocytosis enables error correction in the early embryo. Nature 590, 618-623 (2021).

Tsai, T. Y. et al. An adhesion code ensures robust pattern formation during tissue morphogenesis. Science 370, 113-116 (2020).

Priya, R. et al. Tension heterogeneity directs form and fate to pattern the myocardial wall. Nature 588, 130-134 (2020).

Akieda, Y. et al. Cell competition corrects noisy Wnt morphogen gradients to achieve robust patterning in the zebrafish embryo. Nature Communications 10, 4710 (2019).

Li, X. et al. Systems Properties and Spatiotemporal Regulation of Cell Position Variability during Embryogenesis. Cell Rep 26, 313-321 e317 (2019).

Li, P. et al. Morphogen gradient reconstitution reveals Hedgehog pathway design principles. Science 360, 543-548 (2018).

Xiong, F. et al. Interplay of cell shape and division orientation promotes robust morphogenesis of developing epithelia. Cell 159, 415-427 (2014).

Sulston, J. E., Schierenberg, E., White, J. G. & Thomson, J. N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100, 64-119 (1983).

Cao, J. et al. Establishment of a morphological atlas of the Caenorhabditis elegans embryo using deep-learning-based 4D segmentation. Nat Commun 11, 6254 (2020).

Du, Z., Santella, A., He, F., Tiongson, M. & Bao, Z. De novo inference of systems-level mechanistic models of development from live-imaging-based phenotype analysis. Cell 156, 359-372 (2014).

Richards, J. L., Zacharias, A. L., Walton, T., Burdick, J. T. & Murray, J. I. A quantitative model of normal Caenorhabditis elegans embryogenesis and its disruption after stress. Dev Biol 374, 12-23 (2013).

Moore, J. L., Du, Z. & Bao, Z. Systematic quantification of developmental phenotypes at single-cell resolution during embryogenesis. Development 140, 3266-3274 (2013).

Bao, Z., Zhao, Z., Boyle, T. J., Murray, J. I. & Waterston, R. H. Control of cell cycle timing during C. elegans embryogenesis. Dev Biol 318, 65-72 (2008).

Bao, Z. et al. Automated cell lineage tracing in Caenorhabditis elegans. Proc Natl Acad Sci U S A 103, 2707-2712 (2006).

Lardennois, A. et al. An actin-based viscoplastic lock ensures progressive body-axis elongation. Nature 573, 266-270 (2019).

Hubatsch, L. et al. A cell size threshold limits cell polarity and asymmetric division potential. Nat Phys 15, 1075-1085 (2019).

Jordan, D. J. & Miska, E. A. Canalisation and plasticity on the developmental manifold of Caenorhabditis elegans. Mol Syst Biol 19, e11835 (2023).

Kuang, X. et al. Computable early Caenorhabditis elegans embryo with a phase field model. PLoS Comput Biol 18, e1009755 (2022).

Du, Z. et al. The Regulatory Landscape of Lineage Differentiation in a Metazoan Embryo. Dev Cell 34, 592-607 (2015).

Cinquin, A. et al. Semi-permeable Diffusion Barriers Enhance Patterning Robustness in the C. elegans Germline. Dev Cell 35, 405-417 (2015).

Pohl, C. & Bao, Z. Chiral forces organize left-right patterning in C. elegans by uncoupling midline and anteroposterior axis. Dev Cell 19, 402-412 (2010).

Campos, M. et al. A constant size extension drives bacterial cell size homeostasis. Cell 159, 1433-1446 (2014).

Tanouchi, Y. et al. A noisy linear map underlies oscillations in cell size and gene expression in bacteria. Nature 523, 357-360 (2015).

Large, C. R. L. et al. Lineage-resolved analysis of embryonic gene expression evolution in C. elegans and C. briggsae. Science 388, eadu8249 (2025).

Koyck, L. M. Distributed Lags and Investment Analysis. (North-Holland, 1954).

Lim, H. Y. G. & Plachta, N. Cytoskeletal control of early mammalian development. Nat Rev Mol Cell Biol 22, 548-562 (2021).

SenGupta, S., Parent, C. A. & Bear, J. E. The principles of directed cell migration. Nat Rev Mol Cell Biol 22, 529-547 (2021).

Sandler, O. et al. Lineage correlations of single cell division time as a probe of cell-cycle dynamics. Nature 519, 468-471 (2015).

Naini, F. B. The golden ratio-dispelling the myth. Maxillofac Plast Reconstr Surg 46, 2 (2024).

Rizzo, A. The Golden Ratio Theorem: A Framework for Interchangeability and Self-Similarity in Complex Systems. Advances in Pure Mathematics 13, 559-596 (2023).

Nozari, E. et al. Macroscopic resting-state brain dynamics are best described by linear models. Nat Biomed Eng 8, 68-84 (2024).

Urai, A. E. Structure uncovered: understanding temporal variability in perceptual decision-making. Trends Cogn Sci 30, 54-65 (2026).

Blanco-Duque, C. et al. Oscillatory-Quality of sleep spindles links brain state with sleep regulation and function. Sci Adv 10, eadn6247 (2024).

Lutsker, G. et al. A foundation model for continuous glucose monitoring data. Nature (2026).

Sobral, J. A., Perle, M. & Scheurer, M. S. Physics-informed transformers for electronic quantum states. Nat Commun 16, 10811 (2025).

Liao, S. et al. Temperature-related hospitalization burden under climate change. Nature 644, 960-968 (2025).

Fisman, D. N., Tuite, A. R. & Brown, K. A. Impact of El Niño Southern Oscillation on infectious disease hospitalization risk in the United States. Proceedings of the National Academy of Sciences 113, 14589-14594 (2016).

Chen, G. Y., Gan, M., Wang, S. & Chen, C. L. P. Insights Into Algorithms for Separable Nonlinear Least Squares Problems. IEEE transactions on image processing : a publication of the IEEE Signal Processing Society 30, 1207-1218 (2021).

Olivari, M., Nieuwenhuizen, F. M., Venrooij, J., Bülthoff, H. H. & Pollini, L. Methods for Multiloop Identification of Visual and Neuromuscular Pilot Responses. IEEE Trans Cybern 45, 2780-2791 (2015).

Hutcheon, J. A., Chiolero, A. & Hanley, J. A. Random measurement error and regression dilution bias. Bmj 340, c2289 (2010).

Fitch, D. H. A. Evolution: An Ecological Context for C. elegans. Current Biology 15, R655-R658 (2005).

Giri, S. et al. Evaluation of Daratumumab for the Treatment of Multiple Myeloma in Patients With High-risk Cytogenetic Factors: A Systematic Review and Meta-analysis. JAMA Oncol 6, 1759-1765 (2020).

指标

查看次数: 22

下载次数

附加文件

补充文件

已发布

2026-04-04

如何引用

Wang, J., Xiao, L., Yang, M., Yao, Z., Deng, S., Du, Z., & He, X. (2026). A kinematic equation for the morphogenetic reproducibility of an animal. 浪淘沙预印本平台. https://doi.org/10.65215/LTSpreprints.2026.04.04.000174

利益冲突声明

作者声明无任何需要披露的利益冲突。