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Epigenetic and transcriptional regulation of neuron phenotype. 神经元表型的表观遗传和转录调控。
Pub Date : 2024-08-21 DOI: 10.1387/ijdb.230204ka
Kaia Achim

Understanding the structure and function of cells is central to cell biology and physiology. The ability to control cell function may benefit biomedicine, such as cell-replacement therapy or regeneration. If structure defines function and cells are composed of water, lipids, small metabolites, nucleic acids, and proteins, of which the latter are largely encoded by the DNA present in the same cell, then one may assume that the cell types and variation in cellular phenotypes are shaped by differential gene expression. Cells of the same cell type maintain a similar composition. In this review, I will discuss the epigenetic and transcription regulation mechanisms guiding cell fate- specific gene expression in developing neural cells. Differentiation involves processes of cell-fate selection, commitment and maturation, which are not necessarily coupled.

了解细胞的结构和功能是细胞生物学和生理学的核心。控制细胞功能的能力可能有益于生物医学,如细胞替代疗法或再生。如果说结构决定功能,细胞由水、脂质、小分子代谢物、核酸和蛋白质组成,而后者主要由存在于同一细胞中的 DNA 编码,那么我们可以认为,细胞类型和细胞表型的变化是由不同的基因表达形成的。同一细胞类型的细胞保持着相似的组成。在这篇综述中,我将讨论在发育中的神经细胞中引导细胞命运特异性基因表达的表观遗传和转录调控机制。分化涉及细胞命运选择、承诺和成熟过程,这些过程并不一定相互关联。
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引用次数: 0
Histological characterisation of the horn bud region in 58 day old bovine fetuses. 58 天牛胎儿角芽区的组织学特征。
Pub Date : 2024-08-14 DOI: 10.1387/ijdb.240040ja
Johanna E Aldersey, Tong Chen, Kiro Petrovski, John L Williams, Cynthia D K Bottema

The presence of horns in domestic ruminants, such as cattle, sheep and goats, has financial and welfare implications. The genetic interactions that lead to horn development are not known. Hornless, or polled, cattle occur naturally. The known causative DNA variants (Celtic, Friesian, Mongolian and Guarani) are in intergenic regions on bovine chromosome 1, but their functions are not known. It is thought that horns may be derived from cranial neural crest stem cells and the POLLED variants disrupt the migration or proliferation of these cells. Relaxin family peptide receptor 2 (RXFP2) is more highly expressed in developing horns in cattle compared to nearby skin and has been shown to play a role in horn development in sheep. However, the role of RXFP2 in horn formation is not understood. Histological analyses of cranial tissues from homozygous horned and polled cattle fetuses at day 58 of development was carried out to determine the differences in the structure of the horn bud region. Condensed cells were only observed in the horn bud mesenchyme of horned fetuses and could be the progenitor horn cells. The distribution of neural crest markers (SOX10 and NGFR) and RXFP2 between horned and polled tissues by immunohistochemistry was also analysed. However, SOX10 and NGFR were not detected in the condensed cells, and therefore, these cells are either not derived from the neural crest, or have differentiated and no longer express neural crest markers. SOX10 and NGFR were detected in the peripheral nerves, while RXFP2 was detected in peripheral nerves and in the horn bud epidermis. Previous research has shown that RXFP2 variants are associated with horn phenotypes in cattle an sheep. Therefore, the RXFP2 variants may affect the development of the epidermis or peripheral nerves in the horn bud.

牛、绵羊和山羊等家养反刍动物长角对经济和福利都有影响。导致角发育的基因相互作用尚不清楚。无角牛或花粉牛是自然出现的。已知的致病 DNA 变体(凯尔特、弗里斯兰、蒙古和瓜拉尼)位于牛 1 号染色体的基因间区域,但其功能尚不清楚。据认为,牛角可能来自颅神经嵴干细胞,而 POLLED 变异会破坏这些细胞的迁移或增殖。与附近的皮肤相比,松弛素家族肽受体 2(RXFP2)在牛角发育过程中的表达量更高,并且已被证明在绵羊的角发育过程中发挥作用。然而,RXFP2 在牛角形成过程中的作用尚不清楚。为了确定牛角芽区域结构的差异,我们对发育第 58 天的同卵牛角胎和花粉胎的颅骨组织进行了组织学分析。只有在有角胎儿的角芽间质中观察到凝集细胞,它们可能是原角细胞。免疫组化还分析了神经嵴标记物(SOX10和NGFR)和RXFP2在有角胎儿和花粉胎儿组织中的分布。然而,在凝聚细胞中没有检测到 SOX10 和 NGFR,因此这些细胞要么不是来自神经嵴,要么已经分化,不再表达神经嵴标记。在外周神经中检测到了 SOX10 和 NGFR,而在外周神经和角芽表皮中检测到了 RXFP2。先前的研究表明,RXFP2 变体与牛和羊的角表型有关。因此,RXFP2 变体可能会影响角芽表皮或周围神经的发育。
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引用次数: 0
Genetic targeting of lymphatic endothelial cells in mice: current strategies and future perspectives. 小鼠淋巴内皮细胞的基因靶向:当前策略与未来展望。
Pub Date : 2024-08-12 DOI: 10.1387/ijdb.230215tm
Hans Schoofs, Taija Mäkinen

Lymphatic vessels within different organs have diverse developmental origins, depend on different growth factor signaling pathways for their development and maintenance, and display notable tissue-specific adaptations that contribute to their roles in normal physiology and in various diseases. Functional studies on the lymphatic vasculature rely extensively on the use of mouse models that allow selective gene targeting of lymphatic endothelial cells (LECs). Here, we discuss LEC diversity and provide an overview of some of the commonly used LEC-specific inducible Cre lines and induction protocols, outlining essential experimental parameters and their implications. We describe optimized treatment regimens for embryonic, postnatal and adult LECs, efficiently targeting organs that are commonly studied in lymphatic vascular research, such as the mesentery and skin. We further highlight the anticipated outcomes and limitations associated with each induction scheme and mouse line. The proposed protocols serve as recommendations for laboratories initiating studies involving targeting of the lymphatic vasculature, and aim to promote uniformity in lineage tracing and functional studies within the lymphatic vascular field.

不同器官内的淋巴管具有不同的发育起源,其发育和维持依赖于不同的生长因子信号通路,并显示出明显的组织特异性适应,这有助于它们在正常生理和各种疾病中发挥作用。淋巴管的功能研究广泛依赖于小鼠模型的使用,这种模型允许选择性基因靶向淋巴管内皮细胞(LEC)。在此,我们将讨论淋巴管内皮细胞的多样性,并概述一些常用的淋巴管内皮细胞特异性诱导 Cre 株系和诱导方案,概述基本的实验参数及其影响。我们介绍了针对胚胎、出生后和成年 LEC 的优化治疗方案,有效地针对淋巴管研究中常用的器官,如肠系膜和皮肤。我们进一步强调了与每种诱导方案和小鼠品系相关的预期结果和局限性。建议的方案可作为实验室启动淋巴管靶向研究的推荐方案,旨在促进淋巴管领域的品系追踪和功能研究的统一性。
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引用次数: 0
Origin and Development of Interstitial Cells of Cajal. 卡贾尔间质细胞的起源与发展
Pub Date : 2024-08-12 DOI: 10.1387/ijdb.240057ar
Tara Sweet, Christeen M Abraham, Adam Rich

The digestive tract is a series of organs with specific functions and specialized anatomy. Each organ is organized similarly with concentric layers of epithelial, connective, smooth muscle, and neural tissues. Interstitial cells of Cajal (ICC) are distributed in smooth muscle layers and contribute to the organization of repetitive and rhythmic smooth muscle contractions. Understanding ICC development is critical to understanding gastrointestinal motility patterns. Experiments determining ICC origin and development in mice, chicken, and humans are described, as well as what is known in the zebrafish. At least six types of ICC in the digestive tract have been described and ICC heterogeneity in adult tissues is reviewed. Factors required for ICC development and for maintenance of ICC subclasses are described. This review is suitable for those new to ICC development and physiology, especially those focused on using zebrafish and other model systems.

消化道是一系列具有特殊功能和专门解剖结构的器官。每个器官都有类似的上皮组织、结缔组织、平滑肌和神经组织的同心层。卡贾尔间质细胞(ICC)分布在平滑肌层中,有助于组织平滑肌的重复性和节律性收缩。了解 ICC 的发育对了解胃肠道运动模式至关重要。本文介绍了确定小鼠、鸡和人类 ICC 起源和发育的实验,以及对斑马鱼的了解。已描述了消化道中至少六种类型的 ICC,并回顾了成体组织中 ICC 的异质性。文中还描述了 ICC 发育和维持 ICC 亚类所需的因素。这篇综述适合那些刚接触 ICC 发育和生理学的人,尤其是那些专注于使用斑马鱼和其他模型系统的人。
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引用次数: 0
Expression analysis of thg1l during Xenopus laevis development. thg1l在爪蟾发育过程中的表达分析。
Pub Date : 2024-07-15 DOI: 10.1387/ijdb.240033ma
Davide Martini, Chiara De Cesari, Matteo Digregorio, Alessia Muscò, Guido Giudetti, Martina Giannaccini, Massimiliano Andreazzoli

The tRNA-histidine guanylyltransferase 1-like (THG1L), also known as induced in high glucose-1 (IHG-1), encodes for an essential mitochondria-associated protein highly conserved throughout evolution, that catalyses the 3'-5' addition of a guanine to the 5'-end of tRNA-histidine (tRNAHis). Previous data indicated that THG1L plays a crucial role in the regulation of mitochondrial biogenesis and dynamics, in ATP production, and is critically involved in the modulation of apoptosis, cell-cycle progression and survival, as well as in cellular stress responses and redox homeostasis. Dysregulations of THG1L expression play a central role in various pathologies, including nephropathies, and neurodevelopmental disorders often characterized by developmental delay and cerebellar ataxia. Despite the essential role of THG1L, little is known about its expression during vertebrate development. Herein, we examined the detailed spatio-temporal expression of this gene in the developing Xenopus laevis. Our results show that thg1l is maternally inherited and its temporal expression suggests a role during the earliest stages of embryogenesis. Spatially, thg1l mRNA localizes in the ectoderm and marginal zone mesoderm during early stages of development. Then, at tadpole stages, thg1l transcripts mostly localise in neural crests and their derivatives, somites, developing kidney and central nervous system, therefore largely coinciding with territories displaying intense energy metabolism during organogenesis in Xenopus.

tRNA-histidine guanylyltransferase 1-like (THG1L),又称高糖诱导-1 (IHG-1),编码一种在整个进化过程中高度保守的重要线粒体相关蛋白,它能催化鸟嘌呤在 tRNA-histidine (tRNAHis)的 5'-5' 端进行 3'-5' 添加。以前的数据表明,THG1L 在线粒体生物生成和动态调控、ATP 生成中发挥着关键作用,并在细胞凋亡、细胞周期进展和存活调控以及细胞应激反应和氧化还原平衡中发挥着重要作用。THG1L 表达失调在各种病症中起着核心作用,包括肾病和通常以发育迟缓和小脑共济失调为特征的神经发育疾病。尽管THG1L起着至关重要的作用,但人们对其在脊椎动物发育过程中的表达却知之甚少。在此,我们研究了该基因在发育中的爪蟾中的详细时空表达。我们的研究结果表明,thg1l 是母性遗传的,它在时间上的表达表明它在胚胎发生的最早期阶段发挥作用。在空间上,thg1l mRNA 在发育早期定位于外胚层和边缘区中胚层。然后,在蝌蚪阶段,thg1l转录本主要定位于神经嵴及其衍生物、体节、发育中的肾脏和中枢神经系统,因此在很大程度上与章鱼器官形成过程中能量代谢旺盛的区域相吻合。
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引用次数: 0
Coenocystic oogenesis - modification of or deviation from the germ cell cyst paradigm? 同囊卵生--是对生殖细胞囊范式的修正还是偏离?
Pub Date : 2024-07-09 DOI: 10.1387/ijdb.240064mk
Malgorzata Kloc

Invertebrate and vertebrate species have many unusual cellular structures, such as long- or short-lived cell-in-cell structures and coenocytes. Coenocytes (often incorrectly described as syncytia) are multinuclear cells derived, unlike syncytia, not from the fusion of multiple cells but from multiple nuclear divisions without cytokinesis. An example of a somatic coenocyte is the coenocytic blastoderm in Drosophila. An astonishing property of coenocytes is the ability to differentiate the nuclei sharing a common cytoplasm into different subpopulations with different fate trajectories. An example of a germline coenocyte is the oogenic precursor of appendicularian tunicates, which shares many features with the somatic coenocyte of Drosophila. The germline coenocyte (coenocyst) is quite an unexpected structure because in most animals, including Drosophila, Xenopus, and mice, oogenesis proceeds within a group (cyst, nest) of sibling cells (cystocytes) connected by the intercellular bridges (ring canals, RCs) derived from multiple divisions with incomplete cytokinesis of a progenitor cell called the cystoblast. Here, I discuss the differences and similarities between cystocyte-based and coenocyst-based oogenesis, and the resemblance of coenocystic oogenesis to coenocytic somatic blastoderm in Drosophila. I also describe cell-in-cell structures that although not mechanistically, cytologically, or molecularly connected to somatic or germline coenocytes, are both unorthodox and intriguing cytological phenomena rarely covered by scientific literature.

无脊椎动物和脊椎动物有许多不寻常的细胞结构,例如长寿或短寿的细胞内结构和同源细胞。同源细胞(通常被错误地描述为合胞体)是多核细胞,与合胞体不同,它不是由多个细胞融合而成,而是由多个没有细胞分裂的核分裂而成。果蝇的合核胚层就是体细胞合核的一个例子。同源细胞的一个惊人特性是能够将具有共同细胞质的细胞核分化成具有不同命运轨迹的不同亚群。生殖系同源细胞的一个例子是阑尾鳞茎类动物的卵原前体,它与果蝇的体细胞同源细胞有许多共同之处。生殖同源细胞(同源囊胚)是一种非常出人意料的结构,因为在大多数动物(包括果蝇、爪蟾和小鼠)中,卵子发生都是在同胞细胞(囊胚)群(囊肿、巢)内进行的,同胞细胞由细胞间桥(环管、RC)连接,环管是由一种叫做囊胚细胞的原代细胞在细胞分裂不完全的情况下多次分裂产生的。在这里,我将讨论基于囊胚的卵子发生与基于同源囊胚的卵子发生之间的异同,以及同源囊胚的卵子发生与果蝇同源体细胞胚泡的相似性。我还描述了细胞内结构,虽然这些结构与体细胞或生殖细胞在机械学、细胞学或分子学上没有联系,但它们都是科学文献中很少涉及的非正统和有趣的细胞学现象。
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引用次数: 0
Molecular signaling directing neural plate border formation. 引导神经板边界形成的分子信号。
Pub Date : 2024-07-09 DOI: 10.1387/ijdb.230231me
Mojtaba Esmaeli, Mahdi Barazesh, Zeinab Karimi, Shiva Roshankhah, Ali Ghanbari

During embryonic development, the vertebrate embryonic epiblast is divided into two parts including neural and superficial ectoderm. The neural plate border (NPB) is a narrow transitional area which locates between these parts and contains multipotent progenitor cells. Despite its small size, the cellular heterogeneity in this region produces specific differentiated cells. Signaling pathways, transcription factors, and the expression/repression of certain genes are directly involved in these differentiation processes. Different factors such as the Wnt signaling cascade, fibroblast growth factor (FGF), bone morphogenetic protein (BMP) signaling, and Notch, which are involved in various stages of the growth, proliferation, and differentiation of embryonic cells, are also involved in the determination and differentiation of neural plate border stem cells. Therefore, it is essential to consider the interactions and temporospatial coordination related to cells, tissues, and adjacent structures. This review examines our present knowledge of the formation of the neural plate border and emphasizes the requirement for interaction between different signaling pathways, including the BMP and Wnt cascades, the expression of its special target genes and their regulations, and the precise tissue crosstalk which defines the neural crest fate in the ectoderm at the early human embryonic stages.

在胚胎发育过程中,脊椎动物胚胎上胚层分为两部分,包括神经和表层外胚层。神经板边界(NPB)是位于这两部分之间的狭窄过渡区域,包含多能祖细胞。尽管面积很小,但这一区域的细胞异质性会产生特定的分化细胞。信号通路、转录因子和某些基因的表达/抑制直接参与了这些分化过程。Wnt信号级联、成纤维细胞生长因子(FGF)、骨形态发生蛋白(BMP)信号转导和Notch等不同因子参与了胚胎细胞生长、增殖和分化的各个阶段,它们也参与了神经板边缘干细胞的决定和分化。因此,考虑细胞、组织和邻近结构之间的相互作用和时空协调至关重要。本综述探讨了我们目前对神经板边缘形成的认识,并强调了不同信号通路(包括 BMP 和 Wnt 级联)之间相互作用的要求、其特殊靶基因的表达及其调控,以及在人类胚胎早期外胚层决定神经嵴命运的精确组织串联。
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引用次数: 0
TBC1D24 is likely to regulate vesicle trafficking in glia-like non-sensory epithelial cells of the cochlea. TBC1D24可能调节耳蜗胶质样非感觉上皮细胞的囊泡贩运。
Pub Date : 2024-06-11 DOI: 10.1387/ijdb.240060jd
Jean Defourny

Mutations in the gene encoding Tre2/Bub2/Cdc16 (TBC)1 domain family member 24 (TBC1D24) protein are associated with a variety of neurological disorders, ranging from non-syndromic hearing loss to drug-resistant lethal epileptic encephalopathy and DOORS syndrome [Deafness, Onychodystrophy, Osteodystrophy, intellectual disability (formerly referred to as mental Retardation), and Seizures]. TBC1D24 is a vesicle-associated protein involved in neural crest cell and neuronal migration, maturation, and neurotransmission. In the cochlea, TBC1D24 has been detected in auditory neurons, but few reliable and convergent data exist about the sensory epithelium. Here, the expression of TBC1D24 has been characterized via immunolabelling throughout the postnatal maturation of the mouse cochlear sensory epithelium. TBC1D24 was detected in glia-like non-sensory epithelial cells during early developmental stages. In contrast, TBC1D24 was virtually absent in adjacent sensory hair cells. This expression distinguishing non-sensory from sensory epithelial cells almost disappears around the onset of hearing. Until now, TBC1D24 was mainly described as a neuronal protein either in the brain or in the cochlea. The present observations suggest that TBC1D24 could also regulate vesicle trafficking in cochlear glia-like non-sensory epithelial cells. For a long time, research about epilepsy has been mainly neurocentric. However, there is now evidence proving that glial cell dysregulation contribute to pathogenesis of epilepsy and neurodevelopmental disorders. As a consequence, exploring the possibility that TBC1D24 could also have a role in glial cells of the central nervous system could help to gain insight into TBC1D24-related neurological pathogenesis.

编码 Tre2/Bub2/Cdc16(TBC)1 结构域家族成员 24(TBC1D24)蛋白的基因突变与多种神经系统疾病有关,包括非综合征性听力损失、耐药性致死性癫痫脑病和 DOORS 综合征 [耳聋、肌营养不良、骨营养不良、智力障碍(以前称为智力迟钝)和癫痫发作]。TBC1D24 是一种囊泡相关蛋白,参与神经嵴细胞和神经元的迁移、成熟和神经传递。在耳蜗中,听觉神经元中检测到了 TBC1D24,但有关感觉上皮细胞的可靠和一致的数据却很少。在此,我们通过免疫标记对小鼠耳蜗感觉上皮在整个出生后成熟过程中的 TBC1D24 表达进行了描述。在早期发育阶段,胶质样非感觉上皮细胞中检测到了TBC1D24。相比之下,邻近的感觉毛细胞中几乎没有 TBC1D24。这种区分非感觉上皮细胞和感觉上皮细胞的表达在听力开始时几乎消失。到目前为止,TBC1D24 主要被描述为大脑或耳蜗中的神经元蛋白。目前的观察结果表明,TBC1D24也能调节耳蜗胶质样非感觉上皮细胞的囊泡贩运。长期以来,有关癫痫的研究主要以神经为中心。然而,现在有证据证明,神经胶质细胞失调是癫痫和神经发育障碍的发病机制之一。因此,探索 TBC1D24 在中枢神经系统神经胶质细胞中也发挥作用的可能性,有助于深入了解与 TBC1D24 相关的神经系统发病机制。
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引用次数: 0
Enhancer-promoter communication in Drosophila developmental gene transcription. 果蝇发育基因转录中的增强子-启动子通讯
Pub Date : 2024-06-03 DOI: 10.1387/ijdb.230218gh
George Hunt, Mattias Mannervik

Enhancers play an essential role in gene regulation by receiving cues from transcription factors and relaying these signals to modulate transcription from target promoters. Enhancer-promoter communications occur across large linear distances of the genome and with high specificity. The molecular mechanisms that underlie enhancer-mediated control of transcription remain unresolved. In this review, we focus on research in Drosophila uncovering the molecular mechanisms governing enhancer-promoter communication and discuss the current understanding of developmental gene regulation. The functions of protein acetylation, pausing of RNA polymerase II, transcriptional bursting, and the formation of nuclear hubs in the induction of tissue-specific programs of transcription during zygotic genome activation are considered.

增强子在基因调控中发挥着重要作用,它接收来自转录因子的信号,并将这些信号传递给靶启动子,从而调节靶启动子的转录。增强子与启动子之间的通讯跨越基因组的大线性距离,并具有高度特异性。增强子介导转录控制的分子机制仍未解决。在这篇综述中,我们将重点介绍果蝇研究揭示增强子-启动子通讯分子机制的情况,并讨论目前对发育基因调控的理解。文章探讨了蛋白质乙酰化、RNA聚合酶II的暂停、转录猝灭以及核枢纽的形成在子代基因组激活过程中诱导组织特异性转录程序的功能。
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引用次数: 0
TGF-β signaling molecules in Hydra: role of BMP and BMP inhibitors during pattern formation. 水螅中的 TGF-β 信号分子:BMP 和 BMP 抑制剂在模式形成过程中的作用。
Pub Date : 2024-05-21 DOI: 10.1387/ijdb.240009sg
Lakshmi-Surekha Krishnapati, Surendra Ghaskadbi

Understanding the evolution of body plans has been one of the major areas of investigation in developmental and evolutionary biology. Cnidaria, the sister group to bilaterians, provides an opportunity to elucidate the origin and evolution of body axes. Hydra, a freshwater cnidarian, is a useful model to study signaling pathways governing pattern formation, which are conserved up to vertebrates including humans. The transforming growth factor β (TGF-β) signaling pathway is one of the fundamental pathways that regulate axis formation and organogenesis during embryonic development. In this article, we discuss the TGF-β pathway members identified in Hydra along with other cnidarians with an emphasis on bone morphogenetic proteins (BMPs) and their inhibitors. TGF-β members, especially those involved in BMP signaling pathway, are mainly involved in maintaining the Organizer region and patterning the body axis in Hydra. Identification of other members of this pathway in Hydra and fellow cnidarians would provide insights into the evolution of body axes and pattern formation in more complex metazoans.

了解身体结构的演变一直是发育生物学和进化生物学的主要研究领域之一。两栖类的姊妹类--刺胞动物为阐明体轴的起源和进化提供了机会。淡水刺胞动物水螅(Hydra)是研究支配模式形成的信号通路的有用模型。转化生长因子β(TGF-β)信号通路是胚胎发育过程中调节轴形成和器官形成的基本通路之一。在本文中,我们将讨论在水螅和其他刺胞动物中发现的 TGF-β 通路成员,重点是骨形态发生蛋白(BMPs)及其抑制剂。TGF-β 成员,尤其是那些参与 BMP 信号通路的成员,主要参与维持水螅的器官区和体轴模式化。鉴定水螅和其他刺胞动物中该通路的其他成员将有助于深入了解更复杂的后生动物的体轴和模式形成的进化过程。
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引用次数: 0
期刊
The International journal of developmental biology
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