Hub connectivity, neuronal diversity, and gene expression in the Caenorhabditis elegans connectome.
Hub connectivity, neuronal diversity, and gene expression in the Caenorhabditis elegans connectome.
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DOI：
10.1371/journal.pcbi.1005989
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发表时间：
2018-03
影响因子：
4.3
通讯作者：
Fornito A
中科院分区：
文献类型：
--
作者：
Arnatkevic̆iūtė A;Fulcher BD;Pocock R;Fornito A
神经系统连通性的研究，在各种各样的物种和在不同的分辨率尺度，已经确定了网络组织的几个高度保守的基序。其中一个主题是跨神经元素的连接的异构分布，使得一些元素充当高度连接和功能重要的网络枢纽。这些大脑网络枢纽也紧密相连，形成了一个所谓的富人俱乐部。最近在小鼠身上的研究发现了神经中枢的一个独特的转录特征，其特征是氧化代谢基因的紧密耦合表达，与人类皮层的宏观模间中枢区域相似。在这里，我们试图确定秀丽隐杆线虫神经元连接组的枢纽是否也表现出紧密耦合的基因表达。利用279个秀丽隐杆线虫神经元的化学和电连接的公开数据，以及948个基因中每个神经元的二进制基因表达数据，我们计算了每对神经元的相关基因表达评分，提供了它们基因表达相似性的衡量标准。我们证明中枢神经元之间的连接在基因表达上最相似，而非中枢神经元之间的连接最不相似。对这种影响贡献最大的基因涉及谷氨酸能和胆碱能信号传导以及其他通信过程。我们进一步表明中枢神经元之间的耦合表达不能用它们的神经元亚型（即感觉、运动或中间神经元）、分离距离、化学分泌的神经递质、出生时间、成对谱系距离或它们的拓扑模块关联来解释。相反，这种耦合与大多数中枢作为命令中间神经元的身份有着内在的联系，这是一种调节运动的特定中间神经元。我们的研究结果表明，神经中枢可能具有独特的转录特征，在不同的尺度和物种中保存下来，这与中枢参与调节特定生物体的高阶行为有关。神经系统的一些元素比其他元素拥有更多的连接，这标志着它们是网络枢纽。这些枢纽通常彼此紧密相连，形成一个所谓的富人俱乐部，被认为支持综合功能。最近在老鼠身上的研究表明，连接的中枢比其他成对的大脑区域表现出更高水平的转录耦合。本研究表明，秀丽隐杆线虫的中枢神经元也表现出紧密耦合的基因表达，而这种效应不能用中枢神经元的空间接近性或解剖位置、化学成分、出生时间、神经元谱系或拓扑模块隶属关系来解释。相反，我们发现，秀丽隐杆线虫连接组的大多数枢纽作为命令中间神经元（一种调节运动的特定功能神经元）的身份驱动了共表达的升高。这些发现表明，偶联基因表达是神经中枢高度保守的基因组特征，可能与中枢在更广泛的网络功能中发挥的特定功能作用有关。
Studies of nervous system connectivity, in a wide variety of species and at different scales of resolution, have identified several highly conserved motifs of network organization. One such motif is a heterogeneous distribution of connectivity across neural elements, such that some elements act as highly connected and functionally important network hubs. These brain network hubs are also densely interconnected, forming a so-called rich club. Recent work in mouse has identified a distinctive transcriptional signature of neural hubs, characterized by tightly coupled expression of oxidative metabolism genes, with similar genes characterizing macroscale inter-modular hub regions of the human cortex. Here, we sought to determine whether hubs of the neuronal C. elegans connectome also show tightly coupled gene expression. Using open data on the chemical and electrical connectivity of 279 C. elegans neurons, and binary gene expression data for each neuron across 948 genes, we computed a correlated gene expression score for each pair of neurons, providing a measure of their gene expression similarity. We demonstrate that connections between hub neurons are the most similar in their gene expression while connections between nonhubs are the least similar. Genes with the greatest contribution to this effect are involved in glutamatergic and cholinergic signaling, and other communication processes. We further show that coupled expression between hub neurons cannot be explained by their neuronal subtype (i.e., sensory, motor, or interneuron), separation distance, chemically secreted neurotransmitter, birth time, pairwise lineage distance, or their topological module affiliation. Instead, this coupling is intrinsically linked to the identity of most hubs as command interneurons, a specific class of interneurons that regulates locomotion. Our results suggest that neural hubs may possess a distinctive transcriptional signature, preserved across scales and species, that is related to the involvement of hubs in regulating the higher-order behaviors of a given organism. Some elements of neural systems possess many more connections than others, marking them as network hubs. These hubs are often densely interconnected with each other, forming a so-called rich-club that is thought to support integrated function. Recent work in the mouse suggests that connected pairs of hubs show higher levels of transcriptional coupling than other pairs of brain regions. Here, we show that hub neurons of the nematode C. elegans also show tightly coupled gene expression and that this effect cannot be explained by the spatial proximity or anatomical location of hub neurons, their chemical composition, birth time, neuronal lineage or topological module affiliation. Instead, we find that elevated coexpression is driven by the identity of most hubs of the C. elegans connectome as command interneurons, a specific functional class of neurons that regulate locomotion. These findings suggest that coupled gene expression is a highly conserved genomic signature of neural hubs that may be related to the specific functional role that hubs play in broader network function.
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DOI：
10.1073/pnas.1220826110
发表时间：
2013-07-09
影响因子：
11.1
作者：
Crossley, Nicolas A.;Mechelli, Andrea;Bullmore, Edward T.
通讯作者：
Bullmore, Edward T.
影响因子：
5.3
作者：
Ehaideb, Salleh N.;Wignall, Elizabeth A.;Kasuya, Junko;Evans, William H.;Iyengar, Atulya;Koerselman, Haley L.;Lilienthal, Anthony J.;Bassuk, Alexander G.;Kitamoto, Toshihiro;Manak, J. Robert
通讯作者：
Manak, J. Robert
DOI：
10.1093/brain/awu132
发表时间：
2014-08
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Crossley NA;Mechelli A;Scott J;Carletti F;Fox PT;McGuire P;Bullmore ET
通讯作者：
Bullmore ET
影响因子：
9.2
作者：
Chiang, Ann-Shyn;Lin, Chih-Yung;Hwang, Jenn-Kang
通讯作者：
Hwang, Jenn-Kang
影响因子：
4.3
作者：
Baruch, Leehod;Itzkovitz, Shalev;Segal, Eran
通讯作者：
Segal, Eran