Zhukovsky Mikhail A, Sung Si-Eun, Ott Albrecht
Institute of Endotypes in Oncology, Metabolism, and Immunology "G. Salvatore" (IEOMI), National Research Council (CNR), Via P. Castellino 111, 80131 Naples, Italy.
Biological Experimental Physics, Center for Biophysics, Faculty of Natural Sciences and Technology, Saarland University, Campus B2 1, 66123 Saarbrücken, Germany.
J Dev Biol. 2025 Jul 17;13(3):24. doi: 10.3390/jdb13030024.
Axis definition plays a key role in the establishment of animal body plans, both in normal development and regeneration. The cnidarian can re-establish its simple body plan when regenerating from a random cell aggregate or a sufficiently small tissue fragment. At the beginning of regeneration, a hollow cellular spheroid forms, which then undergoes symmetry breaking and body axis definition. In the past, we have published related work in a physics journal, which is difficult to read for scientists from other disciplines. Here, we review our work for readers not so familiar with this type of approach at a level that requires very little knowledge in mathematics. At the same time, we present a few aspects of biology that we believe to be linked to our work. These biological aspects may be of interest to physicists or members of related disciplines to better understand our approach. The proposed theoretical model is based on fluctuations of gene expression that are triggered by mechanical signaling, leading to increasingly large groups of cells acting in sync. With a single free parameter, the model quantitatively reproduces the experimentally observed expression pattern of the gene , a marker for 'head forming potential'. We observed that positions its axis as a function of a weak temperature gradient, but in a non-intuitive way. Supposing that a large fluctuation including expression is locked to define the head position, the model reproduces this behavior as well-without further changes. We explain why we believe that the proposed fluctuation-based symmetry breaking process agrees well with recent experimental findings where actin filament organization or anisotropic mechanical stimulation act as axis-positioning events. The model suggests that the spheroid exhibits huge sensitivity to external perturbations that will eventually position the axis.
轴的定义在动物身体结构的建立过程中起着关键作用,无论是在正常发育还是再生过程中。刺胞动物能够从随机的细胞聚集体或足够小的组织片段再生时重新建立其简单的身体结构。在再生开始时,会形成一个中空的细胞球体,然后经历对称性破缺和身体轴的定义。过去,我们在一本物理学期刊上发表了相关工作,这对于其他学科的科学家来说很难读懂。在这里,我们以几乎不需要数学知识的水平为不太熟悉这种方法的读者回顾我们的工作。同时,我们介绍一些我们认为与我们的工作相关的生物学方面。这些生物学方面可能会引起物理学家或相关学科成员的兴趣,以便更好地理解我们的方法。所提出的理论模型基于由机械信号触发的基因表达波动,导致越来越多的细胞同步行动。该模型仅用一个自由参数就定量地再现了实验观察到的基因表达模式,该基因是“头部形成潜能”的标志物。我们观察到它将其轴定位为弱温度梯度的函数,但方式并不直观。假设包括其表达在内的一个大波动被锁定以定义头部位置,该模型也能再现这种行为——无需进一步改变。我们解释了为什么我们认为所提出的基于波动的对称性破缺过程与最近的实验结果非常吻合,在这些实验中肌动蛋白丝组织或各向异性机械刺激作为轴定位事件。该模型表明,这个球体对最终会定位轴的外部扰动表现出巨大的敏感性。