Grodstein Joel, Levin Michael
Department of Electrical and Computer Engineering, Tufts University, Medford, Massachusetts, USA.
Allen Discovery Center at Tufts University, Medford, Massachusetts, USA.
Bioelectricity. 2022 Mar 15;4(1):18-30. doi: 10.1089/bioe.2021.0036. eCollection 2022 Mar.
Morphogenesis results when cells cooperate to construct a specific anatomical structure. The behavior of such cell swarms exhibits not only robustness but also plasticity with respect to what specific anatomies will be built. Important aspects of evolutionary biology, regenerative medicine, and cancer are impacted by the algorithms by which instructive information guides invariant or stochastic outcomes of such collective activity. Planarian flatworms are an important model system in this field, as flatworms reliably regenerate a primary body axis after diverse kinds of injury. Importantly, the number of heads to which they regenerate is not determined genetically: lines of worms can be produced, which, with no further manipulation, regenerate as two-headed (2H) worms, or as "Cryptic" worms. When cut into pieces, Cryptic worms produce one-headed (1H) and 2H regenerates stochastically. Neural and bioelectric mechanisms have been proposed to explain aspects of the regenerative dataset. However, these models have not been unified and do not explain all of the Cryptic worm data. In this study, we propose a model in which two separate systems (a bioelectric circuit and a neural polarity mechanism) compete to determine the anatomical structure of a regenerate. We show how our model accounts for existing data and provides a consistent synthesis of mechanisms that explain both the robustness of planarian regeneration and its remarkable re-writability toward novel stable and stochastic anatomical states.
当细胞协作构建特定的解剖结构时,形态发生便会产生。此类细胞群的行为不仅表现出稳健性,而且在构建何种特定解剖结构方面具有可塑性。进化生物学、再生医学和癌症的重要方面受到一些算法的影响,在这些算法中,指导性信息引导着这种集体活动的不变或随机结果。涡虫是该领域的一个重要模型系统,因为涡虫在遭受各种损伤后能可靠地再生出一条主要的身体轴线。重要的是,它们再生出的头部数量并非由基因决定:可以培育出这样的线虫品系,即无需进一步操作,就能再生为双头(2H)线虫,或者再生为“隐性”线虫。当切成片段时,隐性线虫会随机产生单头(1H)和2H再生个体。人们已经提出神经和生物电机制来解释再生数据集的各个方面。然而,这些模型尚未统一,也无法解释所有隐性线虫的数据。在本研究中,我们提出了一个模型,其中两个独立的系统(一个生物电回路和一个神经极性机制)相互竞争,以确定再生个体的解剖结构。我们展示了我们的模型如何解释现有数据,并对各种机制进行了一致的综合,这些机制既解释了涡虫再生的稳健性,也解释了其朝着新的稳定和随机解剖状态的显著可重写性。