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Building, Breaking, and Repairing Neuromuscular Synapses 神经肌肉突触的建立、破坏和修复
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041490
Ruth Herbst, Maartje G. Huijbers, Julien Oury, Steven J. Burden
A coordinated and complex interplay of signals between motor neurons, skeletal muscle cells, and Schwann cells controls the formation and maintenance of neuromuscular synapses. Deficits in the signaling pathway for building synapses, caused by mutations in critical genes or autoantibodies against key proteins, are responsible for several neuromuscular diseases, which cause muscle weakness and fatigue. Here, we describe the role that four key genes, Agrin, Lrp4, MuSK, and Dok7, play in this signaling pathway, how an understanding of their mechanisms of action has led to an understanding of several neuromuscular diseases, and how this knowledge has contributed to emerging therapies for treating neuromuscular diseases.
运动神经元、骨骼肌细胞和许旺细胞之间协调而复杂的信号相互作用,控制着神经肌肉突触的形成和维持。关键基因突变或针对关键蛋白的自身抗体导致突触形成信号通路的缺陷,是导致肌无力和疲劳的多种神经肌肉疾病的原因。在此,我们将介绍 Agrin、Lrp4、MuSK 和 Dok7 这四个关键基因在这一信号通路中的作用,了解这些基因的作用机制如何有助于我们了解几种神经肌肉疾病,以及这些知识如何有助于开发治疗神经肌肉疾病的新疗法。
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引用次数: 0
Neotropics as a Cradle for Adaptive Radiations 新热带地区是适应性辐射的摇篮
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041452
Juan E. Guevara-Andino, Liliana M. Dávalos, Felipe Zapata, María José Endara, Darko D. Cotoras, Jaime Chaves, Santiago Claramunt, Julia López-Delgado, Angela M. Mendoza-Henao, David Salazar-Valenzuela, Gonzalo Rivas-Torres, Justin Yeager
Neotropical ecosystems are renowned for numerous examples of adaptive radiation in both plants and animals resulting in high levels of biodiversity and endemism. However, we still lack a comprehensive review of the abiotic and biotic factors that contribute to these adaptive radiations. To fill this gap, we delve into the geological history of the region, including the role of tectonic events such as the Andean uplift, the formation of the Isthmus of Panama, and the emergence of the Guiana and Brazilian Shields. We also explore the role of ecological opportunities created by the emergence of new habitats, as well as the role of key innovations, such as novel feeding strategies or reproductive mechanisms. We discuss different examples of adaptive radiation, including classic ones like Darwin's finches and Anolis lizards, and more recent ones like bromeliads and lupines. Finally, we propose new examples of adaptive radiations mediated by ecological interactions in their geological context. By doing so, we provide insights into the complex interplay of factors that contributed to the remarkable diversity of life in the Neotropics and highlight the importance of this region in understanding the origins of biodiversity.
新热带生态系统以动植物适应性辐射的众多实例而闻名,这些实例导致了高度的生物多样性和特有性。然而,我们仍然缺乏对促成这些适应性辐射的非生物和生物因素的全面回顾。为了填补这一空白,我们深入研究了该地区的地质历史,包括安第斯隆升、巴拿马地峡的形成以及圭亚那和巴西盾牌的出现等构造事件的作用。我们还探讨了新栖息地的出现所创造的生态机会的作用,以及关键创新(如新的摄食策略或繁殖机制)的作用。我们讨论了适应性辐射的不同范例,包括达尔文雀和阿诺里斯蜥蜴等经典范例,以及凤梨和羽扇豆等最新范例。最后,我们提出了在地质背景下通过生态相互作用实现适应性辐射的新实例。通过这些研究,我们深入了解了各种因素的复杂相互作用,这些因素促成了新热带地区生命的显著多样性,并强调了该地区在理解生物多样性起源方面的重要性。
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引用次数: 0
Glial Cell Development and Function in the Zebrafish Central Nervous System 斑马鱼中枢神经系统神经胶质细胞的发育与功能
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-05-01 DOI: 10.1101/cshperspect.a041350
Tim Czopka, Kelly Monk, Francesca Peri
Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.
过去几十年来,斑马鱼已成为研究神经系统发育、可塑性和再生过程中所有神经胶质细胞类型生物学的绝佳模式生物。在这篇综述中,我们将在 Lyons 和 Talbot 于 2015 年发表的早期研究成果的基础上,总结斑马鱼基因组相对容易操作及其适合体内成像的特性是如何帮助理解神经胶质细胞生物学原理的,重点是少突胶质细胞、小胶质细胞和星形胶质细胞。我们将重点介绍这些神经胶质细胞类型在中枢神经系统中的不同特性和功能的最新发现,并讨论该领域的开放性问题和未来发展方向。
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引用次数: 0
Oligodendrocytes: Myelination, Plasticity, and Axonal Support 少突胶质细胞髓鞘化、可塑性和轴突支持
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-04-15 DOI: 10.1101/cshperspect.a041359
Mikael Simons, Erin M. Gibson, Klaus-Armin Nave
The myelination of axons has evolved to enable fast and efficient transduction of electrical signals in the vertebrate nervous system. Acting as an electric insulator, the myelin sheath is a multilamellar membrane structure around axonal segments generated by the spiral wrapping and subsequent compaction of oligodendroglial plasma membranes. These oligodendrocytes are metabolically active and remain functionally connected to the subjacent axon via cytoplasmic-rich myelinic channels for movement of metabolites and macromolecules to and from the internodal periaxonal space under the myelin sheath. Increasing evidence indicates that oligodendrocyte numbers, specifically in the forebrain, and myelin as a dynamic cellular compartment can both respond to physiological demands, collectively referred to as adaptive myelination. This review summarizes our current understanding of how myelin is generated, how its function is dynamically regulated, and how oligodendrocytes support the long-term integrity of myelinated axons.
在脊椎动物神经系统中,轴突的髓鞘化是为了能够快速有效地传递电信号而演变而来的。作为电绝缘体,髓鞘是轴突节段周围的多层膜结构,由少突胶质细胞浆膜螺旋包裹并随后压实而成。这些少突胶质细胞代谢活跃,并通过富含细胞质的髓鞘通道与邻近轴突保持功能性连接,以便代谢物和大分子进出髓鞘下的节间周围空间。越来越多的证据表明,少突胶质细胞(尤其是前脑中的少突胶质细胞)的数量和髓鞘作为一个动态的细胞区室,都能对生理需求做出反应,统称为适应性髓鞘化。本综述总结了我们目前对髓鞘如何生成、其功能如何动态调节以及少突胶质细胞如何支持髓鞘轴突长期完整性的理解。
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引用次数: 0
Reimagining Cortical Connectivity by Deconstructing Its Molecular Logic into Building Blocks 将分子逻辑解构为积木式构件,重新想象大脑皮层的连接性
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-04-15 DOI: 10.1101/cshperspect.a041509
Xiaoyin Chen
Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene–projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene–projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene–projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene–projection relationship.
全面的神经元连接图为了解神经回路结构奠定了基础。在一个神经回路中,神经元的形态、电生理学、基因表达、活动和其他神经元特性各不相同。因此,要构建全面的连接图,就必须在细胞分辨率上将神经元的各种特性(包括其连接性)联系起来。一种常用的方法是以基因表达谱为锚,将所有其他神经元属性与之关联起来。基因组学和解剖学技术的最新进展极大地提高了确定神经元长程投射并将其与基因表达谱联系起来的能力。这些研究揭示了基因-投射关系中前所未有的细节,但也凸显了在理解这种关系时所面临的概念挑战。在本文中,我将利用最先进的神经解剖学和转录组学技术,深入探讨近期研究的发现和挑战。在此基础上,我提出了一种方法,着重通过基因表达谱和投射的基本特征来理解基因与投射的关系,这些特征分别与潜在的细胞过程相关联。然后,我将讨论投影和基因表达谱的发育轨迹如何带来额外的挑战,以及如何使跨时间的基因-投影关系成为必要。最后,我探讨了一些互补策略,这些策略结合在一起可以为基因-投影关系提供一个全面的视角。
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引用次数: 0
Avian Island Radiations Shed Light on the Dynamics of Adaptive and Nonadaptive Radiation 鸟岛辐射揭示了适应性和非适应性辐射的动态变化
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-04-15 DOI: 10.1101/cshperspect.a041451
Juan Carlos Illera, Juan Carlos Rando, Martim Melo, Luís Valente, Martin Stervander
Understanding the mechanisms underlying species formation and differentiation is a central goal of evolutionary biology and a formidable challenge. This understanding can provide valuable insights into the origins of the astonishing diversity of organisms living on our planet. Avian evolutionary radiations on islands have long fascinated biologists as they provide the ideal variation to study the ecological and evolutionary forces operating on the continuum between incipient lineages to complete speciation. In this review, we summarize the key insights gained from decades of research on adaptive and nonadaptive radiations of both extant and extinct insular bird species. We present a new comprehensive global list of potential avian radiations on oceanic islands, based on published island species checklists, taxonomic studies, and phylogenetic analyses. We demonstrate that our understanding of evolutionary processes is being greatly enhanced through the use of genomic tools. However, to advance the field, it is critical to complement this information with a solid understanding of the ecological and behavioral traits of both extinct and extant avian island species.
了解物种形成和分化的内在机制是进化生物学的核心目标,也是一项艰巨的挑战。这种理解可以为我们地球上生物惊人多样性的起源提供宝贵的见解。长期以来,岛屿上的鸟类进化辐射一直令生物学家着迷,因为它们提供了理想的变异环境,可用于研究从萌芽世系到完全物种分化这一连续过程中的生态和进化力量。在这篇综述中,我们总结了数十年来对现存和已灭绝岛屿鸟类物种的适应性和非适应性辐射研究的主要见解。我们根据已发表的岛屿物种清单、分类学研究和系统发生学分析,提出了一份新的全球海洋岛屿鸟类潜在辐射综合清单。我们表明,通过基因组工具的使用,我们对进化过程的理解正在大大加强。然而,要推进这一领域的研究,关键是要对已灭绝和现存鸟类岛屿物种的生态和行为特征有扎实的了解,以补充这些信息。
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引用次数: 0
Variant Effect Prediction in the Age of Machine Learning 机器学习时代的变异效应预测
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-04-15 DOI: 10.1101/cshperspect.a041467
Yana Bromberg, R. Prabakaran, Anowarul Kabir, Amarda Shehu
Over the years, many computational methods have been created for the analysis of the impact of single amino acid substitutions resulting from single-nucleotide variants in genome coding regions. Historically, all methods have been supervised and thus limited by the inadequate sizes of experimentally curated data sets and by the lack of a standardized definition of variant effect. The emergence of unsupervised, deep learning (DL)-based methods raised an important question: Can machines learn the language of life from the unannotated protein sequence data well enough to identify significant errors in the protein “sentences”? Our analysis suggests that some unsupervised methods perform as well or better than existing supervised methods. Unsupervised methods are also faster and can, thus, be useful in large-scale variant evaluations. For all other methods, however, their performance varies by both evaluation metrics and by the type of variant effect being predicted. We also note that the evaluation of method performance is still lacking on less-studied, nonhuman proteins where unsupervised methods hold the most promise.
多年来,人们创造了许多计算方法,用于分析基因组编码区单核苷酸变异产生的单氨基酸置换的影响。从历史上看,所有方法都是有监督的,因此受到实验数据集规模不足和缺乏变异效应标准化定义的限制。基于深度学习(DL)的无监督方法的出现提出了一个重要问题:机器能否从未注释的蛋白质序列数据中学习到足够好的生命语言,以识别蛋白质 "句子 "中的重大错误?我们的分析表明,一些无监督方法的表现与现有的有监督方法不相上下,甚至更好。无监督方法的速度也更快,因此可用于大规模变异评估。然而,对于所有其他方法来说,它们的性能因评价指标和预测的变异效应类型而异。我们还注意到,对研究较少的非人类蛋白质的方法性能评估仍然缺乏,而无监督方法在这方面最有前途。
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引用次数: 0
Glial Regulation of Circuit Wiring, Firing, and Expiring in the Drosophila Central Nervous System 果蝇中枢神经系统中神经胶质对电路布线、点火和衰竭的调控
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-04-02 DOI: 10.1101/cshperspect.a041347
Jaeda Coutinho-Budd, Marc R. Freeman, Sarah Ackerman
Molecular genetic approaches in small model organisms like Drosophila have helped to elucidate fundamental principles of neuronal cell biology. Much less is understood about glial cells, although interest in using invertebrate preparations to define their in vivo functions has increased significantly in recent years. This review focuses on our current understanding of the three major neuron-associated glial cell types found in the Drosophila central nervous system (CNS)—astrocytes, cortex glia, and ensheathing glia. Together, these cells act like mammalian astrocytes and microglia; they associate closely with neurons including surrounding neuronal cell bodies and proximal neurites, regulate synapses, and engulf neuronal debris. Exciting recent work has shown critical roles for these CNS glial cells in neural circuit formation, function, plasticity, and pathology. As we gain a more firm molecular and cellular understanding of how Drosophila CNS glial cells interact with neurons, it is clear that they share significant molecular and functional attributes with mammalian glia and will serve as an excellent platform for mechanistic studies of glial function.
果蝇等小型模式生物的分子遗传学方法有助于阐明神经细胞生物学的基本原理。尽管近年来人们对使用无脊椎动物制备物来确定其体内功能的兴趣显著增加,但对神经胶质细胞的了解却少得多。本综述重点介绍我们目前对果蝇中枢神经系统(CNS)中发现的三种主要神经元相关胶质细胞类型--胃细胞、皮层胶质细胞和鞘状胶质细胞--的了解。这些细胞的共同作用类似于哺乳动物的星形胶质细胞和小胶质细胞;它们与神经元密切相关,包括围绕神经元细胞体和近端神经元,调节突触,并吞噬神经元碎片。最近令人兴奋的研究表明,这些中枢神经系统胶质细胞在神经回路的形成、功能、可塑性和病理学方面发挥着关键作用。随着我们对果蝇中枢神经系统神经胶质细胞如何与神经元相互作用有了更深入的分子和细胞了解,很明显,它们与哺乳动物的神经胶质细胞有着重要的分子和功能属性,将成为神经胶质细胞功能机理研究的绝佳平台。
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引用次数: 0
Glia Development and Function in the Nematode Caenorhabditis elegans 线虫草履虫神经胶质细胞的发育和功能
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-04-02 DOI: 10.1101/cshperspect.a041346
Aakanksha Singhvi, Shai Shaham, Georgia Rapti
The nematode Caenorhabditis elegans is a powerful experimental setting for uncovering fundamental tenets of nervous system organization and function. Its nearly invariant and simple anatomy, coupled with a plethora of methodologies for interrogating single-gene functions at single-cell resolution in vivo, have led to exciting discoveries in glial cell biology and mechanisms of glia–neuron interactions. Findings over the last two decades reinforce the idea that insights from C. elegans can inform our understanding of glial operating principles in other species. Here, we summarize the current state-of-the-art, and describe mechanistic insights that have emerged from a concerted effort to understand C. elegans glia. The remarkable acceleration in the pace of discovery in recent years paints a portrait of striking molecular complexity, exquisite specificity, and functional heterogeneity among glia. Glial cells affect nearly every aspect of nervous system development and function, from generating neurons, to promoting neurite formation, to animal behavior, and to whole-animal traits, including longevity. We discuss emerging questions where C. elegans is poised to fill critical knowledge gaps in our understanding of glia biology.
线虫是揭示神经系统组织和功能基本原理的强大实验环境。它的解剖结构近乎不变且简单,再加上大量在体内以单细胞分辨率检测单基因功能的方法,使得神经胶质细胞生物学和神经胶质细胞-神经元相互作用机制有了令人兴奋的发现。过去二十年的研究结果强化了这样一种观点,即从 elegans 中获得的见解可以帮助我们理解其他物种的神经胶质细胞工作原理。在此,我们总结了当前的最新研究成果,并描述了在理解优雅小鼠神经胶质细胞的共同努力中获得的机理启示。近年来,神经胶质细胞的发现速度明显加快,为我们描绘了一幅神经胶质细胞具有惊人的分子复杂性、精致的特异性和功能异质性的画卷。神经胶质细胞几乎影响着神经系统发育和功能的方方面面,从产生神经元、促进神经元形成、动物行为到整个动物的特征,包括寿命。我们将讨论一些新出现的问题,在这些问题上,蛇尾藻有望填补我们对神经胶质生物学认识的关键知识空白。
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引用次数: 0
How Important Is Sexual Isolation to Speciation? 性隔离对物种繁衍有多重要?
IF 7.2 2区 生物学 Q1 CELL BIOLOGY Pub Date : 2024-04-01 DOI: 10.1101/cshperspect.a041427
Kerry L Shaw, Christopher R Cooney, Tamra C Mendelson, Michael G Ritchie, Natalie S Roberts, Leeban H Yusuf

A central role for sexual isolation in the formation of new species and establishment of species boundaries has been noticed since Darwin and is frequently emphasized in the modern literature on speciation. However, an objective evaluation of when and how sexual isolation plays a role in speciation has been carried out in few taxa. We discuss three approaches for assessing the importance of sexual isolation relative to other reproductive barriers, including the relative evolutionary rate of sexual trait differentiation, the relative strength of sexual isolation in sympatry, and the role of sexual isolation in the long-term persistence of diverging forms. First, we evaluate evidence as to whether sexual isolation evolves faster than other reproductive barriers during the early stages of divergence. Second, we discuss available evidence as to whether sexual isolation is as strong or stronger than other barriers between closely related sympatric species. Finally, we consider the effect of sexual isolation on long-term species persistence, relative to other reproductive barriers. We highlight challenges to our knowledge of and opportunities to improve upon our understanding of sexual isolation from different phases of the speciation process.

自达尔文以来,人们就注意到性隔离在新物种的形成和物种边界的确立中发挥着核心作用,现代关于物种分化的文献也经常强调这一点。然而,对于性隔离何时以及如何在物种形成中发挥作用,很少有分类群进行过客观的评估。我们讨论了评估性隔离相对于其他生殖障碍的重要性的三种方法,包括性状分化的相对进化速度、共生中性隔离的相对强度以及性隔离在分化形式的长期持续中的作用。首先,我们评估了在分化早期阶段性隔离是否比其他生殖障碍进化得更快的证据。其次,我们讨论现有的证据,以确定在亲缘关系很近的同域物种之间,性隔离是否与其他障碍一样强或更强。最后,我们考虑了相对于其他生殖障碍而言,性隔离对物种长期存在的影响。我们强调了在物种形成过程的不同阶段,我们对性隔离的认识所面临的挑战和改进的机会。
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引用次数: 0
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Cold Spring Harbor perspectives in biology
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