Department of Computer Science, University of Surrey, Guildford, GU2 7XH, UK.
Biosciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Cereb Cortex. 2021 Jun 10;31(7):3237-3253. doi: 10.1093/cercor/bhab003.
One of the most characteristic properties of many vertebrate neural systems is the layered organization of different cell types. This cytoarchitecture exists in the cortex, the retina, the hippocampus, and many other parts of the central nervous system. The developmental mechanisms of neural layer formation have been subject to substantial experimental efforts. Here, we provide a general computational model for cortical layer formation in 3D physical space. We show that this multiscale, agent-based model, comprising two distinct stages of apoptosis, can account for the wide range of neuronal numbers encountered in different cortical areas and species. Our results demonstrate the phenotypic richness of a basic state diagram structure. Importantly, apoptosis allows for changing the thickness of one layer without automatically affecting other layers. Therefore, apoptosis increases the flexibility for evolutionary change in layer architecture. Notably, slightly changed gene regulatory dynamics recapitulate the characteristic properties observed in neurodevelopmental diseases. Overall, we propose a novel computational model using gene-type rules, exhibiting many characteristics of normal and pathological cortical development.
许多脊椎动物神经系统的最显著特征之一是不同细胞类型的分层组织。这种细胞结构存在于皮质、视网膜、海马体和中枢神经系统的许多其他部位。神经层形成的发育机制已经受到大量实验的关注。在这里，我们提供了一个用于三维物理空间皮质层形成的通用计算模型。我们表明，这种多尺度、基于代理的模型，包含两个不同的凋亡阶段，可以解释在不同皮质区域和物种中遇到的广泛神经元数量。我们的结果表明了基本状态图结构的表型丰富性。重要的是，凋亡允许改变一层的厚度而不会自动影响其他层。因此，凋亡增加了在层结构中进化变化的灵活性。值得注意的是，略微改变基因调控动力学可以重现神经发育疾病中观察到的特征。总体而言，我们提出了一个使用基因类型规则的新的计算模型，表现出正常和病理皮质发育的许多特征。
