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Identification and characterization of GAL4 drivers that mark distinct cell types and regions in the Drosophila adult gut. 在果蝇成年肠道中标记不同细胞类型和区域的GAL4驱动因子的鉴定和表征。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2021-03-01 Epub Date: 2020-12-16 DOI: 10.1080/01677063.2020.1853722
Seung Yeon Lim, Hyejin You, Jinhyeong Lee, Jaejin Lee, Yoojin Lee, Kyung-Ah Lee, Boram Kim, Ji-Hoon Lee, JiHyeon Jeong, Sooin Jang, Byoungsoo Kim, Hyungjun Choi, Gayoung Hwang, Min Sung Choi, Sung-Eun Yoon, Jae Young Kwon, Won-Jae Lee, Young-Joon Kim, Greg S B Suh

The gastrointestinal tract in the adult Drosophila serves as a model system for exploring the mechanisms underlying digestion, absorption and excretion, stem cell plasticity, and inter-organ communication, particularly through the gut-brain axis. It is also useful for studying the cellular and adaptive responses to dietary changes, alterations in microbiota and immunity, and systematic and endocrine signals. Despite the various cell types and distinct regions in the gastrointestinal tract, few tools are available to target and manipulate the activity of each cell type and region, and their gene expression. Here, we report 353 GAL4 lines and several split-GAL4 lines that are expressed in enteric neurons (ENs), progenitors (ISCs and EBs), enterocytes (ECs), enteroendocrine cells (EEs), or/and other cell types that are yet to be identified in distinct regions of the gut. We had initially collected approximately 600 GAL4 lines that may be expressed in the gut based on RNA sequencing data, and then crossed them to UAS-GFP to perform immunohistochemistry to identify those that are expressed selectively in the gut. The cell types and regional expression patterns that are associated with the entire set of GAL4 drivers and split-GAL4 combinations are annotated online at http://kdrc.kr/index.php (K-Gut Project). This GAL4 resource can be used to target specific populations of distinct cell types in the fly gut, and therefore, should permit a more precise investigation of gut cells that regulate important biological processes.

成年果蝇的胃肠道是探索消化、吸收和排泄、干细胞可塑性和器官间通信(特别是通过肠-脑轴)机制的模型系统。它还有助于研究细胞对饮食变化、微生物群和免疫的改变以及系统和内分泌信号的适应性反应。尽管胃肠道中存在多种细胞类型和不同的区域,但很少有工具可用于靶向和操纵每种细胞类型和区域的活性及其基因表达。在这里,我们报告了353个GAL4系和几个分裂GAL4系,它们在肠神经元(ENs)、祖细胞(ISCs和EBs)、肠细胞(ECs)、肠内分泌细胞(EEs)或/和其他尚未在肠道不同区域确定的细胞类型中表达。我们最初根据RNA测序数据收集了大约600个可能在肠道中表达的GAL4系,然后将它们与UAS-GFP杂交,进行免疫组化,以鉴定那些在肠道中选择性表达的GAL4系。与整套GAL4驱动因子和分裂-GAL4组合相关的细胞类型和区域表达模式在http://kdrc.kr/index.php (K-Gut Project)上进行了在线注释。这种GAL4资源可用于针对苍蝇肠道中不同细胞类型的特定群体,因此,应该允许对调节重要生物过程的肠道细胞进行更精确的研究。
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引用次数: 7
A journey to 'tame a small metazoan organism', seen through the artistic eyes of C. elegans researchers. 从 elegans 研究人员的艺术视角看 "驯服小型后生动物 "之旅‡。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-09-01 Epub Date: 2020-12-08 DOI: 10.1080/01677063.2020.1839449
Eleni Gourgou, Alexandra R Willis, Sebastian Giunti, Maria J De Rosa, Amanda G Charlesworth, Mirella Hernandez Lima, Elizabeth Glater, Sonja Soo, Bianca Pereira, Kübra Akbaş, Anushka Deb, Madhushree Kamak, Mark W Moyle, Annika Traa, Aakanksha Singhvi, Surojit Sural, Eugene Jennifer Jin

In the following pages, we share a collection of photos, drawings, and mixed-media creations, most of them especially made for this JoN issue, manifesting C. elegans researchers' affection for their model organism and the founders of the field. This is a celebration of our community's growth, flourish, spread, and bright future. Descriptions provided by the contributors, edited for space. 1.

在接下来的篇幅中,我们将与您分享一组照片、图画和混合媒体创作,其中大部分都是为本期 JoN 特别制作的,它们表达了 elegans 研究人员对其模式生物和该领域奠基人的深厚感情。这是对我们社区的成长、繁荣、传播和美好未来的庆祝。投稿者提供的说明,因篇幅所限,有删减。1.
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引用次数: 4
Nature's gift to neuroscience. 大自然给神经科学的礼物
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-09-01 DOI: 10.1080/01677063.2020.1841760
Joy Alcedo, Yishi Jin, Douglas S Portman, Veena Prahlad, David Raizen, Georgia Rapti, X Z Shawn Xu, Yun Zhang, Chun-Fang Wu
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引用次数: 1
Studying neural circuits of decision-making in Drosophila larva. 果蝇幼虫决策神经回路的研究。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-03-01 Epub Date: 2020-02-13 DOI: 10.1080/01677063.2020.1719407
Tihana Jovanic

To study neural circuits underlying decisions, the model organism used for that purpose has to be simple enough to be able to dissect the circuitry neuron by neuron across the nervous system and in the same time complex enough to be able to perform different types of decisions. Here, I lay out the case: (1) that Drosophila larva is an advantageous model system that balances well these two requirements and (2) the insights gained from this model, assuming that circuit principles may be shared across species, can be used to advance our knowledge of neural circuit implementation of decision-making in general, including in more complex brains.

为了研究决策背后的神经回路,用于这一目的的模型生物必须足够简单,以便能够在神经系统中一个神经元一个神经元地解剖回路,同时足够复杂,以便能够执行不同类型的决策。在这里,我列出了这个案例:(1)果蝇幼虫是一个有利的模型系统,它很好地平衡了这两个要求;(2)从这个模型中获得的见解,假设电路原理可能在物种之间共享,可以用来提高我们对决策的神经回路实现的认识,包括在更复杂的大脑中。
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引用次数: 3
Studying complex brain dynamics using Drosophila. 用果蝇研究复杂的大脑动力学。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-03-01 Epub Date: 2019-12-26 DOI: 10.1080/01677063.2019.1706092
Sophie Aimon, Ilona C Grunwald Kadow

The field has successfully used Drosophila genetic tools to identify neurons and sub-circuits important for specific functions. However, for an organism with complex and changing internal states to succeed in a complex and changing natural environment, many neurons and circuits need to interact dynamically. Drosophila's many advantages, combined with new imaging tools, offer unique opportunities to study how the brain functions as a complex dynamical system. We give an overview of complex activity patterns and how they can be observed, as well as modeling strategies, adding proof of principle in some cases.

该领域已经成功地使用果蝇遗传工具来识别对特定功能重要的神经元和亚回路。然而,对于具有复杂和不断变化的内部状态的生物体来说,要在复杂和不断变化的自然环境中取得成功,许多神经元和电路需要动态地相互作用。果蝇的许多优势,加上新的成像工具,为研究大脑作为一个复杂的动力系统如何运作提供了独特的机会。我们概述了复杂的活动模式,以及如何观察它们,以及建模策略,并在某些情况下添加了原理证明。
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引用次数: 4
Understanding neurobehavioral genetics of zebrafish. 了解斑马鱼的神经行为遗传学。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-03-01 Epub Date: 2020-01-05 DOI: 10.1080/01677063.2019.1698565
Sergey V Cheresiz, Andrey D Volgin, Alexandra Kokorina Evsyukova, Alim A O Bashirzade, Konstantin A Demin, Murilo S de Abreu, Tamara G Amstislavskaya, Allan V Kalueff

Due to its fully sequenced genome, high genetic homology to humans, external fertilization, fast development, transparency of embryos, low cost and active reproduction, the zebrafish (Danio rerio) has become a novel promising model organism in biomedicine. Zebrafish are a useful tool in genetic and neuroscience research, including linking various genetic mutations to brain mechanisms using forward and reverse genetics. These approaches have produced novel models of rare genetic CNS disorders and common brain illnesses, such as addiction, aggression, anxiety and depression. Genetically modified zebrafish also foster neuroanatomical studies, manipulating neural circuits and linking them to different behaviors. Here, we discuss recent advances in neurogenetics of zebrafish, and evaluate their unique strengths, inherent limitations and the rapidly growing potential for elucidating the conserved roles of genes in neuropsychiatric disorders.

斑马鱼具有基因组全测序、与人类基因同源性高、体外受精、发育快、胚胎透明、成本低、繁殖活跃等特点,已成为生物医学领域一种前景广阔的新型模式生物。斑马鱼是遗传和神经科学研究的有用工具,包括使用正向和反向遗传学将各种基因突变与大脑机制联系起来。这些方法已经产生了罕见的遗传性中枢神经系统疾病和常见脑部疾病的新模型,如成瘾、攻击、焦虑和抑郁。转基因斑马鱼也促进了神经解剖学的研究,操纵神经回路并将它们与不同的行为联系起来。在这里,我们讨论了斑马鱼神经遗传学的最新进展,并评估了它们独特的优势,固有的局限性和快速增长的潜力,以阐明基因在神经精神疾病中的保守作用。
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引用次数: 13
The Unc13A isoform is important for phasic release and olfactory memory formation at mushroom body synapses. un13a异构体在蘑菇体突触的相释放和嗅觉记忆形成中起重要作用。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-03-01 Epub Date: 2020-01-24 DOI: 10.1080/01677063.2019.1710146
Jennifer Woitkuhn, Anatoli Ender, Christine B Beuschel, Marta Maglione, Tanja Matkovic-Rachid, Sheng Huang, Martin Lehmann, Joerg R P Geiger, Stephan J Sigrist

The cellular analysis of mushroom body (MB)-dependent memory forming processes is far advanced, whereas, the molecular and physiological understanding of their synaptic basis lags behind. Recent analysis of the Drosophila olfactory system showed that Unc13A, a member of the M(Unc13) release factor family, promotes a phasic, high release probability component, while Unc13B supports a slower tonic release component, reflecting their different nanoscopic positioning within individual active zones. We here use STED super-resolution microscopy of MB lobe synapses to show that Unc13A clusters closer to the active zone centre than Unc13B. Unc13A specifically supported phasic transmission and short-term plasticity of Kenyon cell:output neuron synapses, measured by combining electrophysiological recordings of output neurons with optogenetic stimulation. Knockdown of unc13A within Kenyon cells provoked drastic deficits of olfactory aversive short-term and anaesthesia-sensitive middle-term memory. Knockdown of unc13B provoked milder memory deficits. Thus, a low frequency domain transmission component is probably crucial for the proper representation of memory-associated activity patterns, consistent with sparse Kenyon cell activation during memory acquisition and retrieval. Notably, Unc13A/B ratios appeared highly diversified across MB lobes, leaving room for an interplay of activity components in memory encoding and retrieval.

对蘑菇体(MB)依赖性记忆形成过程的细胞分析非常先进,而对其突触基础的分子和生理理解却很落后。最近对果蝇嗅觉系统的分析表明,作为M(Unc13)释放因子家族的一员,Unc13A促进一种相位性、高释放概率的成分,而Unc13B支持一种较慢的tonic释放成分,这反映了它们在个体活性区的纳米级定位不同。我们使用STED超分辨率显微镜观察MB叶突触,发现Unc13A簇比Unc13B簇更靠近活跃区中心。un13a特别支持Kenyon细胞:输出神经元突触的相位传递和短期可塑性,通过结合输出神经元的电生理记录和光遗传刺激来测量。在Kenyon细胞中敲低unc13A会引起嗅觉厌恶短期记忆和麻醉敏感中期记忆的严重缺陷。敲除un13b会引起较轻的记忆缺陷。因此,低频域传输组件可能对记忆相关活动模式的正确表示至关重要,这与记忆获取和检索过程中稀疏的凯尼恩细胞激活一致。值得注意的是,un13a /B比率在MB叶中表现出高度多样化,这为记忆编码和检索中的活动成分的相互作用留下了空间。
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引用次数: 4
Experimental psychology meets behavioral ecology: what laboratory studies of learning polymorphisms mean for learning under natural conditions, and vice versa. 实验心理学符合行为生态学:学习多态性的实验室研究对自然条件下的学习意味着什么,反之亦然。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-03-01 Epub Date: 2020-02-06 DOI: 10.1080/01677063.2020.1718674
Brian H Smith, Chelsea N Cook

Behavior genetics, and specifically the study of learning and memory, has benefitted immensely from the development of powerful forward- and reverse-genetic methods for investigating the relationships between genes and behavior. Application of these methods in controlled laboratory settings has led to insights into gene-behavior relationships. In this perspective article, we argue that the field is now poised to make significant inroads into understanding the adaptive value of heritable variation in behavior in natural populations. Studies of natural variation with several species, in particular, are now in a position to complement laboratory studies of mechanisms, and sometimes this work can lead to counterintuitive insights into the mechanism of gene action on behavior. We make this case using a recent example from work with the honey bee, Apis mellifera.

行为遗传学,特别是学习和记忆的研究,极大地受益于研究基因和行为之间关系的强大的正向和反向遗传方法的发展。这些方法在受控实验室环境中的应用已经导致了对基因-行为关系的见解。在这篇前瞻性文章中,我们认为该领域现在准备在理解自然种群中行为遗传变异的适应价值方面取得重大进展。特别是对几个物种的自然变异的研究,现在可以补充实验室对机制的研究,有时这项工作可以导致对基因作用于行为的机制的反直觉的见解。我们用最近的一个关于蜜蜂的例子来说明这个问题。
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引用次数: 5
A biographical sketch of Troy D. Zars (1967-2018). 特洛伊·d·扎尔斯(1967-2018)的传记小品。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-03-01 DOI: 10.1080/01677063.2020.1716749
Bertram Gerber, Elizabeth G King, Divya Sitaraman

Troy D. Zars (1967-2018) was an American biologist. He studied the relationships between genes, neuronal circuits and behavior in the fruit fly Drosophila melanogaster. Zars co-pioneered the use of transgene expression to locally restore gene function in memory-defective fly mutants, an approach that provided breakthrough insights into the localization of memory traces in the fly brain. With ensuing refinements of the methods of transgene expression and the broadening in the range of transgenes to be expressed, this shaped the field of modern behavioral neurogenetics.

特洛伊·扎尔斯(Troy D. Zars, 1967-2018),美国生物学家。他研究了黑腹果蝇的基因、神经回路和行为之间的关系。Zars共同开创了使用转基因表达来局部恢复记忆缺陷果蝇突变体的基因功能的方法,这种方法为果蝇大脑中记忆痕迹的定位提供了突破性的见解。随着随后转基因表达方法的改进和转基因表达范围的扩大,这形成了现代行为神经遗传学领域。
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引用次数: 0
Oxytocin ameliorates bone cancer pain by suppressing toll-like receptor 4 and proinflammatory cytokines in rat spinal cord. 催产素通过抑制大鼠脊髓toll样受体4和促炎细胞因子改善骨癌疼痛。
IF 1.9 4区 医学 Q3 GENETICS & HEREDITY Pub Date : 2020-03-01 Epub Date: 2020-03-02 DOI: 10.1080/01677063.2019.1711077
Xiaping Mou, Ji Fang, An Yang, Gang Du

Bone cancer pain is considered to be mechanistically unique compared with inflammatory or neuropathic pain states. Toll-like receptor 4 (TLR4) is a transmembrane receptor protein which has been reported to be involved in neuropathic pain. However, the role of TLR4 in bone cancer pain is still unclear. Therefore, the aim of this study is to investigate the hypothesis that oxytocin may ameliorate bone cancer pain by suppressing TLR4 in spinal cord. Behavioral analysis and molecular biological experiments were carried out. Our data demonstrated that intrathecally delivery of oxytocin significantly ameliorated the mechanical allodynia and thermal hyperalgesia in bone cancer pain rats. Moreover, oxytocin suppressed the up-regulation of TLR4 and proinflammatory cytokines TNFα and IL-1β in spinal cord of bone cancer pain rats. Therefore, we concluded that intrathecal administration of oxytocin relieves bone cancer pain by suppressing the up-regulation of TLR4, TNFα and IL-1β in spinal cord. Oxytocin possesses analgesic efficacy against bone cancer pain and deserves further to confirm its effectiveness in clinically relevant of cancer pain.

与炎性或神经性疼痛状态相比,骨癌疼痛被认为在机制上是独特的。toll样受体4 (TLR4)是一种跨膜受体蛋白,已被报道参与神经性疼痛。然而,TLR4在骨癌疼痛中的作用尚不清楚。因此,本研究的目的是探讨催产素可能通过抑制脊髓TLR4来改善骨癌疼痛的假设。进行行为分析和分子生物学实验。我们的数据表明,鞘内注入催产素可显著改善骨癌痛大鼠的机械异常性痛和热痛觉过敏。此外,催产素抑制了骨癌痛大鼠脊髓中TLR4和促炎因子TNFα、IL-1β的上调。因此,我们认为鞘内注射催产素通过抑制脊髓中TLR4、TNFα和IL-1β的上调来缓解骨癌疼痛。催产素对骨癌性疼痛具有镇痛作用,其在癌痛相关临床中的有效性有待进一步证实。
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引用次数: 11
期刊
Journal of neurogenetics
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