论文标题

关闭形态发生的循环:通过闭环反应扩散的形态发生数学模型

Closing the Loop on Morphogenesis: A Mathematical Model of Morphogenesis by Closed-Loop Reaction-Diffusion

论文作者

Grodstein, Joel, Levin, Michael

论文摘要

形态发生,是细胞组对新兴复合物解剖结构的建立和修复,是一个引人入胜且与生物医学相关的问题。它最吸引人的方面之一是,发育中的胚胎可以从干扰中可靠地恢复,例如分成双胞胎。尽管这种可靠性意味着在形态学领域中最小化某种类型的寻求目标误差,但就这种过程的详细,建设性的模型而言,有许多差距被用于实施蜂窝群的集体智能。我们描述了一种用于创建具有高可靠性的反应扩散(RD)模式的闭环负反馈系统。它使用细胞自动机表征形态学模式,然后将其与目标进行比较并进行相应调整,从而为解剖稳态建模和稳健的靶标形态提供了一个框架。具体来说,我们创建了一个带有n个重复的RD模式,其中n很容易改变。此外,在遗传控制下,可以很容易地将RD模式的单个重复伸展或缩小,例如,某些形态学特征比其他形态特征更大。最后,细胞自动机使用计算波,该计算波在单向上扫描形态学模式,以表征负反馈然后控制的特征。通过利用先前的过程不对称地建立平面极性(例如头部与尾巴),我们的自动机已经大大简化了。这项工作有助于理解形态计算的设计原理的激动人心的努力,这些努力可用于了解进化的发展机制,在再生医学环境中操纵它们,或将一定程度的合成智能嵌入到新颖的生物工程结构中。

Morphogenesis, the establishment and repair of emergent complex anatomy by groups of cells, is a fascinating and biomedically-relevant problem. One of its most fascinating aspects is that a developing embryo can reliably recover from disturbances, such as splitting into twins. While this reliability implies some type of goal-seeking error minimization over a morphogenic field, there are many gaps with respect to detailed, constructive models of such a process being used to implement the collective intelligence of cellular swarms. We describe a closed-loop negative-feedback system for creating reaction-diffusion (RD) patterns with high reliability. It uses a cellular automaton to characterize a morphogen pattern, then compares it to a goal and adjusts accordingly, providing a framework for modeling anatomical homeostasis and robust generation of target morphologies. Specifically, we create a RD pattern with N repetitions, where N is easily changeable. Furthermore, the individual repetitions of the RD pattern can be easily stretched or shrunk under genetic control to create, e.g., some morphological features larger than others. Finally, the cellular automaton uses a computation wave that scans the morphogen pattern unidirectionally to characterize the features that the negative feedback then controls. By taking advantage of a prior process asymmetrically establishing planar polarity (e.g., head vs. tail), our automaton is greatly simplified. This work contributes to the exciting effort of understanding design principles of morphological computation, which can be used to understand evolved developmental mechanisms, manipulate them in regenerative medicine settings, or embed a degree of synthetic intelligence into novel bioengineered constructs.

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