Gap Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms.
Gap Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms.
复制标题
DOI：
10.3390/ijms161126065
复制
发表时间：
2015-11-24
影响因子：
5.6
通讯作者：
Levin M
中科院分区：
文献类型：
--
作者：
Emmons-Bell M;Durant F;Hammelman J;Bessonov N;Volpert V;Morokuma J;Pinet K;Adams DS;Pietak A;Lobo D;Levin M
动物身体计划的形状是由基因组编码的蛋白质成分构建的。然而，由许多细胞类型组成的生物电网络具有其自身的内在动力学，并且可以在胚胎发生和再生过程中驱动不同的形态结果。涡虫扁虫因其再生能力而成为探索身体计划模式的流行系统，但尽管有大量关于干细胞分化和基本轴向模式的分子信息，但人们对如何产生不同的头部形状知之甚少。在这里，我们发现，在 G. dorotocephala 断头后，细胞间生理连通性的短暂扰动（使用间隙连接阻断剂辛醇）可以导致再生头部形状完全不同，随机匹配其他已知的涡虫物种（S. mediterranea、D. japonica 和 P. felina）。我们使用形态计量分析来量化生理网络扰动从同一基因组诱导不同物种特异性头部形状的能力。此外，我们提出了一种基于计算代理的再生过程中的细胞和物理动力学模型，可以定量地再现观察到的形状变化。基因组野生型 G. dorotocephala 在再生过程中诱导的形态学改变不仅包括头部的形状，还包括大脑的形态、成体干细胞（新生细胞）的特征分布以及前部组织内静息电位的生物电梯度。有趣的是，形状的变化并不是永久性的；再生完成后，完整的动物会在最初完全再生后的第二个重塑阶段中，在几周内重塑回适合 G. dorotocephala 的头部形状。我们提出了一个概念模型来指导未来的工作，以描述生物电网络在一小组离散头部形态中随机选择的分子机制。总而言之，这些数据和分析揭示了形态信息在决定物种特异性形状方面的重要生理修饰因素，并揭示它们是再生涡虫头部模式的新的指导性输入。
The shape of an animal body plan is constructed from protein components encoded by the genome. However, bioelectric networks composed of many cell types have their own intrinsic dynamics, and can drive distinct morphological outcomes during embryogenesis and regeneration. Planarian flatworms are a popular system for exploring body plan patterning due to their regenerative capacity, but despite considerable molecular information regarding stem cell differentiation and basic axial patterning, very little is known about how distinct head shapes are produced. Here, we show that after decapitation in G. dorotocephala, a transient perturbation of physiological connectivity among cells (using the gap junction blocker octanol) can result in regenerated heads with quite different shapes, stochastically matching other known species of planaria (S. mediterranea, D. japonica, and P. felina). We use morphometric analysis to quantify the ability of physiological network perturbations to induce different species-specific head shapes from the same genome. Moreover, we present a computational agent-based model of cell and physical dynamics during regeneration that quantitatively reproduces the observed shape changes. Morphological alterations induced in a genomically wild-type G. dorotocephala during regeneration include not only the shape of the head but also the morphology of the brain, the characteristic distribution of adult stem cells (neoblasts), and the bioelectric gradients of resting potential within the anterior tissues. Interestingly, the shape change is not permanent; after regeneration is complete, intact animals remodel back to G. dorotocephala-appropriate head shape within several weeks in a secondary phase of remodeling following initial complete regeneration. We present a conceptual model to guide future work to delineate the molecular mechanisms by which bioelectric networks stochastically select among a small set of discrete head morphologies. Taken together, these data and analyses shed light on important physiological modifiers of morphological information in dictating species-specific shape, and reveal them to be a novel instructive input into head patterning in regenerating planaria.