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Uncovering the Embryonic Origins of Duchenne Muscular Dystrophy. 揭示杜兴氏肌肉萎缩症的胚胎起源。
IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-10-23 DOI: 10.1002/wsbm.1653
Philip Barrett, Ke'ale W Louie, Jean-Baptiste Dupont, David L Mack, Lisa Maves

Duchenne muscular dystrophy (DMD) is a severe degenerative muscle disease caused by mutations in the DMD gene, which encodes dystrophin. Despite its initial description in the late 19th century by French neurologist Guillaume Duchenne de Boulogne, and identification of causal DMD genetic mutations in the 1980s, therapeutics remain challenging. The current standard of care is corticosteroid treatment, which delays the progression of muscle dysfunction but is associated with significant adverse effects. Emerging therapeutic approaches, including AAV-mediated gene transfer, CRISPR gene editing, and small molecule interventions, are under development but face considerable obstacles. Although DMD is viewed as a progressive muscle disease, muscle damage and abnormal molecular signatures are already evident during fetal myogenesis. This early onset of pathology suggests that the limited success of current therapies may partly be due to their administration after aberrant embryonic myogenesis has occurred in the absence of dystrophin. Consequently, identifying optimal therapeutic strategies and intervention windows for DMD may depend on a better understanding of the earliest DMD disease mechanisms. As newer techniques are applied, the field is gaining increasingly detailed insights into the early muscle developmental abnormalities in DMD. A comprehensive understanding of the initial events in DMD pathogenesis and progression will facilitate the generation and testing of effective therapeutic interventions.

杜氏肌营养不良症(DMD)是一种严重的退行性肌肉疾病,由编码肌营养不良蛋白的 DMD 基因突变引起。尽管法国神经学家纪尧姆-杜兴-德-布洛涅(Guillaume Duchenne de Boulogne)在 19 世纪末首次描述了这种疾病,并在 20 世纪 80 年代确定了导致 DMD 的基因突变,但治疗方法仍然充满挑战。目前的标准疗法是皮质类固醇治疗,这种疗法可延缓肌肉功能障碍的发展,但会产生严重的不良反应。包括 AAV 介导的基因转移、CRISPR 基因编辑和小分子干预在内的新兴治疗方法正在开发中,但面临着相当大的障碍。虽然 DMD 被认为是一种进行性肌肉疾病,但在胎儿肌肉形成过程中,肌肉损伤和异常分子特征就已显现。这种早期发病的病理现象表明,目前的疗法之所以收效甚微,部分原因可能是这些疗法是在缺乏肌营养不良蛋白的情况下,在胚胎肌生成发生异常后才开始使用的。因此,确定 DMD 的最佳治疗策略和干预窗口可能取决于更好地了解 DMD 最早的发病机制。随着新技术的应用,该领域对 DMD 早期肌肉发育异常的了解越来越详细。全面了解 DMD 发病和进展的初始事件将有助于产生和测试有效的治疗干预措施。
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引用次数: 0
SLC40A1 in iron metabolism, ferroptosis, and disease: A review. 铁代谢、铁变态反应和疾病中的 SLC40A1:综述。
IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-01 Epub Date: 2024-03-20 DOI: 10.1002/wsbm.1644
Yan Zhang, Liyi Zou, Xiaodan Li, Long Guo, Baoguang Hu, Hua Ye, Yi Liu

Solute carrier family 40 member 1 (SLC40A1) plays an essential role in transporting iron from intracellular to extracellular environments. When SLC40A1 expression is abnormal, cellular iron metabolism becomes dysregulated, resulting in an overload of intracellular iron, which induces cell ferroptosis. Numerous studies have confirmed that ferroptosis is closely associated with the development of many diseases. Here, we review recent findings on SLC40A1 in ferroptosis and its association with various diseases, intending to explore new directions for research on disease pathogenesis and new therapeutic targets for prevention and treatment. This article is categorized under: Cancer > Genetics/Genomics/Epigenetics Metabolic Diseases > Molecular and Cellular Physiology.

溶质运载家族 40 成员 1(SLC40A1)在将铁从细胞内转运到细胞外环境中发挥着重要作用。当 SLC40A1 表达异常时,细胞铁代谢就会失调,导致细胞内铁超载,从而诱发细胞铁变态反应。大量研究证实,铁突变与许多疾病的发生密切相关。在此,我们综述了最近关于 SLC40A1 在铁氧化过程中的作用及其与多种疾病相关的研究结果,旨在探索疾病发病机制研究的新方向以及预防和治疗的新靶点。本文归类于癌症 > 遗传学/基因组学/表观遗传学 代谢性疾病 > 分子和细胞生理学。
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引用次数: 0
Advances in understanding immune homeostasis in latent tuberculosis infection. 在了解潜伏结核感染的免疫稳态方面取得的进展。
IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-07-01 Epub Date: 2024-02-13 DOI: 10.1002/wsbm.1643
Liangfei Niu, Hao Wang, Geyang Luo, Jing Zhou, Zhidong Hu, Bo Yan

Nearly one-fourth of the global population is infected by Mycobacterium tuberculosis (Mtb), and approximately 90%-95% remain asymptomatic as latent tuberculosis infection (LTBI), an estimated 5%-10% of those with latent infections will eventually progress to active tuberculosis (ATB). Although it is widely accepted that LTBI transitioning to ATB results from a disruption of host immune balance and a weakening of protective immune responses, the exact underlying immunological mechanisms that promote this conversion are not well characterized. Thus, it is difficult to accurately predict tuberculosis (TB) progression in advance, leaving the LTBI population as a significant threat to TB prevention and control. This article systematically explores three aspects related to the immunoregulatory mechanisms and translational research about LTBI: (1) the distinct immunocytological characteristics of LTBI and ATB, (2) LTBI diagnostic markers discovery related to host anti-TB immunity and metabolic pathways, and (3) vaccine development focus on LTBI. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology Infectious Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Genetics/Genomics/Epigenetics.

全球近四分之一的人口感染了结核分枝杆菌(Mtb),约 90%-95% 的人无症状,处于结核病潜伏感染(LTBI)状态,估计有 5%-10% 的潜伏感染者最终会发展为活动性结核病(ATB)。虽然人们普遍认为,LTBI 向 ATB 的转变是宿主免疫平衡被破坏和保护性免疫反应减弱的结果,但促进这种转变的确切潜在免疫机制还没有得到很好的描述。因此,很难提前准确预测肺结核(TB)的进展情况,这就使得LTBI人群成为肺结核防控的重大威胁。本文从三个方面系统地探讨了LTBI的免疫调节机制和转化研究:(1)LTBI和ATB不同的免疫细胞学特征;(2)与宿主抗结核免疫和代谢途径相关的LTBI诊断标记物的发现;(3)LTBI疫苗的研发重点。本文归类于传染病 > 分子和细胞生理学 传染病 > 遗传学/基因组学/表观遗传学 免疫系统疾病 > 遗传学/基因组学/表观遗传学。
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引用次数: 0
The intersection of virus infection and liver disease: A comprehensive review of pathogenesis, diagnosis, and treatment. 病毒感染与肝病的交集:全面回顾发病机制、诊断和治疗。
IF 4.6 3区 医学 Q2 Medicine Pub Date : 2024-05-01 Epub Date: 2024-01-22 DOI: 10.1002/wsbm.1640
Meng Ren, Chenxia Lu, Mingwei Zhou, Xiaobing Jiang, Xiaodong Li, Ningning Liu

Liver disease represents a significant global burden, placing individuals at a heightened risk of developing cirrhosis and liver cancer. Viral infections act as a primary cause of liver diseases on a worldwide scale. Infections involving hepatitis viruses, notably hepatitis B, C, and E viruses, stand out as the most prevalent contributors to acute and chronic intrahepatic adverse outcome, although the hepatitis C virus (HCV) can be effectively cured with antiviral drugs, but no preventative vaccination developed. Hepatitis B virus (HBV) and HCV can lead to both acute and chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC), which are principal causes of worldwide morbidity and mortality. Other viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), are capable of causing liver damage. Therefore, it is essential to recognize that virus infections and liver diseases are intricate and interconnected processes. A profound understanding of the underlying relationship between virus infections and liver diseases proves pivotal in the effective prevention, diagnosis, and treatment of these conditions. In this review, we delve into the mechanisms by which virus infections induce liver diseases, as well as explore the pathogenesis, diagnosis, and treatment of liver diseases. This article is categorized under: Infectious Diseases > Biomedical Engineering.

肝脏疾病是全球的一个重大负担,它使人们面临罹患肝硬化和肝癌的更高风险。在全球范围内,病毒感染是导致肝病的主要原因。虽然丙型肝炎病毒(HCV)可以通过抗病毒药物有效治愈,但目前还没有开发出预防性疫苗,因此,肝炎病毒(尤其是乙型、丙型和戊型肝炎病毒)感染是造成急性和慢性肝内不良后果的最主要因素。乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)可导致急性和慢性肝病,包括肝硬化和肝细胞癌(HCC),它们是全球发病率和死亡率的主要原因。其他病毒,如 Epstein-Barr 病毒 (EBV) 和巨细胞病毒 (CMV),也能造成肝损伤。因此,必须认识到病毒感染和肝脏疾病是错综复杂、相互关联的过程。深刻理解病毒感染与肝脏疾病之间的内在关系,对于有效预防、诊断和治疗这些疾病至关重要。在这篇综述中,我们将深入探讨病毒感染诱发肝病的机制,并探讨肝病的发病机制、诊断和治疗。本文归类于传染病 > 生物医学工程。
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引用次数: 0
Review of cardiac-coronary interaction and insights from mathematical modeling. 回顾心脏与冠状动脉的相互作用以及数学建模的启示。
IF 4.6 3区 医学 Q2 Medicine Pub Date : 2024-05-01 Epub Date: 2024-02-05 DOI: 10.1002/wsbm.1642
Lei Fan, Haifeng Wang, Ghassan S Kassab, Lik Chuan Lee

Cardiac-coronary interaction is fundamental to the function of the heart. As one of the highest metabolic organs in the body, the cardiac oxygen demand is met by blood perfusion through the coronary vasculature. The coronary vasculature is largely embedded within the myocardial tissue which is continually contracting and hence squeezing the blood vessels. The myocardium-coronary vessel interaction is two-ways and complex. Here, we review the different types of cardiac-coronary interactions with a focus on insights gained from mathematical models. Specifically, we will consider the following: (1) myocardial-vessel mechanical interaction; (2) metabolic-flow interaction and regulation; (3) perfusion-contraction matching, and (4) chronic interactions between the myocardium and coronary vasculature. We also provide a discussion of the relevant experimental and clinical studies of different types of cardiac-coronary interactions. Finally, we highlight knowledge gaps, key challenges, and limitations of existing mathematical models along with future research directions to understand the unique myocardium-coronary coupling in the heart. This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Biomedical Engineering Cardiovascular Diseases > Molecular and Cellular Physiology.

心脏与冠状动脉的相互作用是心脏功能的基础。作为人体新陈代谢最旺盛的器官之一,心脏对氧气的需求是通过冠状动脉血管的血液灌注来满足的。冠状血管主要位于心肌组织内,心肌组织不断收缩,从而挤压血管。心肌与冠状动脉血管之间的相互作用是双向和复杂的。在此,我们将回顾不同类型的心肌-冠状动脉相互作用,并重点介绍从数学模型中获得的启示。具体来说,我们将考虑以下几点:(1)心肌-血管机械相互作用;(2)代谢-血流相互作用和调节;(3)灌注-收缩匹配;以及(4)心肌和冠状动脉血管之间的慢性相互作用。我们还讨论了不同类型心脏与冠状动脉相互作用的相关实验和临床研究。最后,我们强调了现有数学模型的知识差距、主要挑战和局限性,以及未来的研究方向,以了解心脏中独特的心肌-冠状动脉耦合。本文归类于心血管疾病 > 计算模型 心血管疾病 > 生物医学工程 心血管疾病 > 分子和细胞生理学。
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引用次数: 0
The yeast-human coevolution: Fungal transition from passengers, colonizers, and invaders. 酵母菌与人类的共同进化:真菌从旅客、殖民者到入侵者的转变。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2024-05-01 Epub Date: 2023-12-26 DOI: 10.1002/wsbm.1639
Stefano Nenciarini, Sonia Renzi, Monica di Paola, Niccolò Meriggi, Duccio Cavalieri

Fungi are the cause of more than a billion infections in humans every year, although their interactions with the host are still neglected compared to bacteria. Major systemic fungal infections are very unusual in the healthy population, due to the long history of coevolution with the human host. Humans are routinely exposed to environmental fungi and can host a commensal mycobiota, which is increasingly considered as a key player in health and disease. Here, we review the current knowledge on host-fungi coevolution and the factors that regulate their interaction. On one hand, fungi have learned to survive and inhabit the host organisms as a natural ecosystem, on the other hand, the host immune system finely tunes the response toward fungi. In turn, recognition of fungi as commensals or pathogens regulates the host immune balance in health and disease. In the human gut ecosystem, yeasts provide a fingerprint of the transient microbiota. Their status as passengers or colonizers is related to the integrity of the gut barrier and the risk of multiple disorders. Thus, the study of this less known component of the microbiota could unravel the rules of the transition from passengers to colonizers and invaders, as well as their dependence on the innate component of the host's immune response. This article is categorized under: Infectious Diseases > Environmental Factors Immune System Diseases > Environmental Factors Infectious Diseases > Molecular and Cellular Physiology.

尽管与细菌相比,真菌与宿主之间的相互作用仍被忽视,但每年真菌造成的人类感染超过 10 亿例。由于真菌与人类宿主共同进化的历史悠久,在健康人群中,重大的全身性真菌感染非常罕见。人类经常接触环境中的真菌,并能寄生共生真菌生物群,而真菌生物群越来越被认为是影响健康和疾病的关键因素。在此,我们回顾了目前关于宿主与真菌共同进化的知识以及调节它们之间相互作用的因素。一方面,真菌学会了生存并栖息在作为自然生态系统的宿主生物体内;另一方面,宿主的免疫系统对真菌的反应进行了微调。反过来,将真菌识别为共生菌还是病原体,又调节着宿主在健康和疾病中的免疫平衡。在人类肠道生态系统中,酵母菌是瞬时微生物群的指纹。它们是客体还是定植者,与肠道屏障的完整性和多种疾病的风险有关。因此,对微生物群中这种鲜为人知的成分进行研究,可以揭示从旅客到定植者和入侵者的过渡规则,以及它们对宿主免疫反应先天成分的依赖性。本文归类于传染病 > 环境因素 免疫系统疾病 > 环境因素 传染病 > 分子和细胞生理学。
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引用次数: 0
Ascomycetes yeasts: The hidden part of human microbiome. 子囊菌酵母:人类微生物组的隐藏部分
IF 4.6 3区 医学 Q2 Medicine Pub Date : 2024-05-01 Epub Date: 2024-01-16 DOI: 10.1002/wsbm.1641
Stefano Nenciarini, Sonia Renzi, Monica di Paola, Niccolò Meriggi, Duccio Cavalieri

The fungal component of the microbiota, the mycobiota, has been neglected for a long time due to its poor richness compared to bacteria. Limitations in fungal detection and taxonomic identification arise from using metagenomic approaches, often borrowed from bacteriome analyses. However, the relatively recent discoveries of the ability of fungi to modulate the host immune response and their involvement in human diseases have made mycobiota a fundamental component of the microbial communities inhabiting the human host, deserving some consideration in host-microbe interaction studies and in metagenomics. Here, we reviewed recent data on the identification of yeasts of the Ascomycota phylum across human body districts, focusing on the most representative genera, that is, Saccharomyces and Candida. Then, we explored the key factors involved in shaping the human mycobiota across the lifespan, ranging from host genetics to environment, diet, and lifestyle habits. Finally, we discussed the strengths and weaknesses of culture-dependent and independent methods for mycobiota characterization. Overall, there is still room for some improvements, especially regarding fungal-specific methodological approaches and bioinformatics challenges, which are still critical steps in mycobiota analysis, and to advance our knowledge on the role of the gut mycobiota in human health and disease. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Environmental Factors Infectious Diseases > Environmental Factors.

微生物区系中的真菌区系(mycobiota)长期以来一直被忽视,因为与细菌相比,真菌区系的丰富程度较低。真菌检测和分类鉴定的局限性来自于元基因组学方法,这种方法通常是从细菌组分析中借鉴过来的。然而,最近发现真菌具有调节宿主免疫反应的能力并参与人类疾病,这使得真菌生物群成为栖息在人类宿主中的微生物群落的基本组成部分,值得在宿主-微生物相互作用研究和元基因组学中加以考虑。在此,我们回顾了最近鉴定人体各部位子囊菌门酵母菌的数据,重点是最具代表性的属,即酵母菌属和念珠菌属。然后,我们探讨了从宿主遗传到环境、饮食和生活习惯等影响人一生中霉菌生物群的关键因素。最后,我们讨论了霉菌生物群特征描述中依赖培养和独立培养方法的优缺点。总之,我们仍有改进的余地,尤其是在真菌特异性方法学和生物信息学方面的挑战,这些仍是霉菌生物群分析的关键步骤,也是推进我们对肠道霉菌生物群在人类健康和疾病中的作用的认识的关键步骤。本文归类于免疫系统疾病 > 遗传学/基因组学/表观遗传学 免疫系统疾病 > 环境因素 传染性疾病 > 环境因素。
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引用次数: 0
The noncanonical NFκB pathway: Regulatory mechanisms in health and disease. 非正则 NFκB 通路:健康与疾病的调控机制
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2024-04-18 DOI: 10.1002/wsbm.1646
Benancio N Rodriguez, Helen Huang, Jennifer J Chia, Alexander Hoffmann
The noncanonical NFκB signaling pathway mediates the biological functions of diverse cell survival, growth, maturation, and differentiation factors that are important for the development and maintenance of hematopoietic cells and immune organs. Its dysregulation is associated with a number of immune pathologies and malignancies. Originally described as the signaling pathway that controls the NFκB family member RelB, we now know that noncanonical signaling also controls NFκB RelA and cRel. Here, we aim to clarify our understanding of the molecular network that mediates noncanonical NFκB signaling and review the human diseases that result from a deficient or hyper-active noncanonical NFκB pathway. It turns out that dysregulation of RelA and cRel, not RelB, is often implicated in mediating the resulting pathology. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Cancer > Molecular and Cellular Physiology Immune System Diseases > Stem Cells and Development.
非正则 NFκB 信号通路介导多种细胞存活、生长、成熟和分化因子的生物功能,这些因子对造血细胞和免疫器官的发育和维持非常重要。它的失调与多种免疫疾病和恶性肿瘤有关。非典型信号传导最初被描述为控制 NFκB 家族成员 RelB 的信号传导途径,现在我们知道非典型信号传导还控制 NFκB RelA 和 cRel。 在此,我们旨在澄清我们对介导非典型 NFκB 信号传导的分子网络的理解,并回顾因非典型 NFκB 通路缺乏或过度活跃而导致的人类疾病。结果发现,RelA 和 cRel 而非 RelB 的失调往往与介导由此产生的病理现象有关。本文归类于免疫系统疾病 > 分子与细胞生理学 癌症 > 分子与细胞生理学 免疫系统疾病 > 干细胞与发育。
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引用次数: 0
Sex differences in CD8+ T cell responses during adaptive immunity. 适应性免疫过程中 CD8+ T 细胞反应的性别差异。
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2024-04-05 DOI: 10.1002/wsbm.1645
Paul Jerard Layug, Harman Vats, Kamali Kannan, J. Arsenio
Biological sex is an important variable that influences the immune system's susceptibility to infectious and non-infectious diseases and their outcomes. Sex dimorphic features in innate and adaptive immune cells and their activities may help to explain sex differences in immune responses. T lymphocytes in the adaptive immune system are essential to providing protection against infectious and chronic inflammatory diseases. In this review, T cell responses are discussed with focus on the current knowledge of biological sex differences in CD8+ T cell mediated adaptive immune responses in infectious and chronic inflammatory diseases. Future directions aimed at investigating the molecular and cellular mechanisms underlying sex differences in diverse T cell responses will continue to underscore the significance of understanding sex differences in protective immunity at the cellular level, to induce appropriate T cell-based immune responses in infection, autoimmunity, and cancer. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Infectious Diseases > Molecular and Cellular Physiology.
生物性别是影响免疫系统对传染性和非传染性疾病的易感性及其结果的一个重要变量。先天性和适应性免疫细胞的性别二形特征及其活动可能有助于解释免疫反应的性别差异。适应性免疫系统中的 T 淋巴细胞对预防感染性和慢性炎症性疾病至关重要。本综述讨论了 T 细胞的反应,重点是目前对 CD8+ T 细胞介导的适应性免疫反应在传染病和慢性炎症性疾病中的生物学性别差异的认识。未来研究各种 T 细胞反应中性别差异的分子和细胞机制的方向将继续强调从细胞水平了解保护性免疫中性别差异的重要性,从而在感染、自身免疫和癌症中诱导适当的基于 T 细胞的免疫反应。本文归类于免疫系统疾病 > 分子和细胞生理学 传染性疾病 > 分子和细胞生理学。
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引用次数: 0
Let's talk about sex: Mechanisms of neural sexual differentiation in Bilateria. 让我们来谈谈性:双尾目动物神经性分化的机制
IF 3.1 3区 医学 Q2 Medicine Pub Date : 2024-03-01 Epub Date: 2024-01-07 DOI: 10.1002/wsbm.1636
Emma C Roggenbuck, Elijah A Hall, Isabel B Hanson, Alyssa A Roby, Katherine K Zhang, Kyle A Alkatib, Joseph A Carter, Jarred E Clewner, Anna L Gelfius, Shiyuan Gong, Finley R Gordon, Jolene N Iseler, Samhita Kotapati, Marilyn Li, Areeba Maysun, Elise O McCormick, Geetanjali Rastogi, Srijani Sengupta, Chantal U Uzoma, Madison A Wolkov, E Josephine Clowney

In multicellular organisms, sexed gonads have evolved that facilitate release of sperm versus eggs, and bilaterian animals purposefully combine their gametes via mating behaviors. Distinct neural circuits have evolved that control these physically different mating events for animals producing eggs from ovaries versus sperm from testis. In this review, we will describe the developmental mechanisms that sexually differentiate neural circuits across three major clades of bilaterian animals-Ecdysozoa, Deuterosomia, and Lophotrochozoa. While many of the mechanisms inducing somatic and neuronal sex differentiation across these diverse organisms are clade-specific rather than evolutionarily conserved, we develop a common framework for considering the developmental logic of these events and the types of neuronal differences that produce sex-differentiated behaviors. This article is categorized under: Congenital Diseases > Stem Cells and Development Neurological Diseases > Stem Cells and Development.

在多细胞生物中,已进化出促进精子和卵子释放的性别性腺,两栖动物通过交配行为有目的地结合配子。对于从卵巢产生卵子和从睾丸产生精子的动物来说,已经进化出不同的神经回路来控制这些物理上不同的交配行为。在这篇综述中,我们将描述两栖动物的三个主要支系--涡虫纲、蝶形目和嗜光目--的神经回路性分化的发育机制。虽然这些不同生物体内诱导体细胞和神经元性别分化的许多机制是特定类群而非进化保守的,但我们建立了一个共同的框架来考虑这些事件的发育逻辑以及产生性别分化行为的神经元差异类型。本文归类于先天性疾病 > 干细胞与发育 神经系统疾病 > 干细胞与发育。
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引用次数: 0
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