Center for Neural Informatics, Structures, and Plasticity and Neuroscience Program, Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA 22030, USA.
Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA.
Int J Mol Sci. 2023 Apr 4;24(7):6741. doi: 10.3390/ijms24076741.
Dendritic morphology underlies the source and processing of neuronal signal inputs. Morphology can be broadly described by two types of geometric characteristics. The first is dendrogram topology, defined by the length and frequency of the arbor branches; the second is spatial embedding, mainly determined by branch angles and straightness. We have previously demonstrated that microtubules and actin filaments are associated with arbor elongation and branching, fully constraining dendrogram topology. Here, we relate the local distribution of these two primary cytoskeletal components with dendritic spatial embedding. We first reconstruct and analyze 167 sensory neurons from the larva encompassing multiple cell classes and genotypes. We observe that branches with a higher microtubule concentration tend to deviate less from the direction of their parent branch across all neuron types. Higher microtubule branches are also overall straighter. F-actin displays a similar effect on angular deviation and branch straightness, but not as consistently across all neuron types as microtubule. These observations raise the question as to whether the associations between cytoskeletal distributions and arbor geometry are sufficient constraints to reproduce type-specific dendritic architecture. Therefore, we create a computational model of dendritic morphology purely constrained by the cytoskeletal composition measured from real neurons. The model quantitatively captures both spatial embedding and dendrogram topology across all tested neuron groups. These results suggest a common developmental mechanism regulating diverse morphologies, where the local cytoskeletal distribution can fully specify the overall emergent geometry of dendritic arbors.
树突形态学是神经元信号输入的来源和处理基础。形态学可以用两种类型的几何特征来广泛描述。第一种是树突图拓扑结构，由树突分支的长度和频率定义；第二种是空间嵌入，主要由分支角度和直线度决定。我们之前已经证明微管和肌动蛋白丝与树突伸长和分支有关，完全约束了树突图拓扑结构。在这里，我们将这两种主要细胞骨架成分的局部分布与树突的空间嵌入联系起来。我们首先重建和分析了 167 个来自幼虫的感觉神经元，这些神经元包含多个细胞类群和基因型。我们观察到，在所有神经元类型中，微管浓度较高的分支偏离其母分支方向的程度较小。较高的微管分支也更直。F-肌动蛋白对角度偏差和分支直线度的影响类似，但不如微管那样在所有神经元类型中都一致。这些观察结果提出了一个问题，即细胞骨架分布和树突几何形状之间的关联是否足以重现特定类型的树突结构。因此，我们创建了一个纯粹由从真实神经元中测量的细胞骨架组成来约束的树突形态学计算模型。该模型在所有测试的神经元组中都能定量地捕捉空间嵌入和树突图拓扑结构。这些结果表明存在一种共同的发育机制来调节多样化的形态，其中局部细胞骨架分布可以完全指定树突分支总体的涌现几何形状。
