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Valproic acid effects on human adipose-derived stem cell differentiation into oligodendrocytes and improved remyelination in a mouse model of Multiple Sclerosis. 丙戊酸对人类脂肪来源的干细胞分化为少突胶质细胞的影响以及改善多发性硬化小鼠模型中的髓鞘再形成。
Pub Date : 2023-01-01 DOI: 10.1387/ijdb.230154ng
Sahar Ghosouri, Mohammad Bakhtiari, Soleimani Mitra, Nazem Ghasemi

Valproic acid (VPA), a neuroprotective agent and inhibitor of GSK3-β, along with human Adipose-Derived Stem Cells (hADSCs) have been proposed to be potential therapeutic agents for neurodegenerative disorders. In the present study, we have assessed the effects of VPA alone or in combination with hADSCs on oligodendrocyte differentiation, remyelination, and functional recovery in a mouse model of Multiple Sclerosis (MS). These MS-model mice were randomly divided into cuprizone, sham, VPA, hADSC, and VPA/hADSC groups, with 10 mice considered a control group (healthy mice). The hanging wire test was used to measure motor behavior. To estimate the level of myelination, we performed toluidine blue staining and immunofluorescent staining for OLIG2 and MOG-positive cells. Real-time PCR was used to evaluate the expression of β-catenin, human and mouse Mbp, Mog, and Olig2 genes. Remyelination and motor function improved in mice receiving VPA, hADSCs, and especially VPA/hADSCs compared to the Cup and Sham groups (P < 0.01). Additionally, the number of MOG and OLIG2 positive cells significantly increased in the VPA/hADSCs group compared to the Cup and Sham groups (P < 0.01). The expression of β-catenin, myelin and the other oligodendrocyte-specific genes was significantly higher in the VPA recipient groups. Valproic acid can enhance the differentiation of stem cells into oligodendrocytes, making it a potential candidate for MS treatment.

丙戊酸(VPA)是一种神经保护剂和GSK3-β抑制剂,与人脂肪来源干细胞(hADSCs)一起被认为是神经退行性疾病的潜在治疗剂。在本研究中,我们评估了VPA单独或与hADSCs联合对多发性硬化症(MS)小鼠模型中少突胶质细胞分化、髓鞘再生和功能恢复的影响。将这些MS模型小鼠随机分为Cupizone、sham、VPA、hADSC和VPA/hADSC组,其中10只小鼠被视为对照组(健康小鼠)。吊线测试用于测量电机行为。为了估计髓鞘形成的水平,我们对OLIG2和MOG阳性细胞进行了甲苯胺蓝染色和免疫荧光染色。实时PCR用于评估β-连环蛋白、人和小鼠Mbp、Mog和Olig2基因的表达。与Cup和Sham组相比,接受VPA、hADSCs,尤其是VPA/hADSCs的小鼠的脱髓鞘和运动功能得到改善(P<0.01)。此外,与Cup组和Sham对照组相比,VPA/hADS组的MOG和OLIG2阳性细胞数量显著增加(P<0.01),髓鞘和其他少突胶质细胞特异性基因在VPA受体组中显著更高。丙戊酸可以增强干细胞向少突胶质细胞的分化,使其成为MS治疗的潜在候选药物。
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引用次数: 0
The stem cell transcription factor ZFP296 transforms NIH3T3 cells and promotes anchorage-independent growth of cancer cells. 干细胞转录因子ZFP296可转化NIH3T3细胞,并促进癌细胞的锚定依赖性生长。
Pub Date : 2023-01-01 DOI: 10.1387/ijdb.230143hk
Yumi Mizoue, Tomomi Ikeda, Takako Ikegami, Oleksandra Riabets, Yoshie Oishi, Morikuni Tobita, Hidenori Akutsu, Koichi Hattori, Beate Heissig, Hiroshi Koide

Cancer cells and embryonic stem (ES) cells share several biological properties, suggesting that some genes expressed in ES cells may play an important role in cancer cell growth. In this study, we investigated the possible role of zinc finger protein 296 (ZFP296), a transcription factor expressed in ES cells, in cancer development. First, we found that overexpression of Zfp296 in NIH3T3 mouse fibroblasts induced two phenomena indicative of cell transformation: enhanced proliferation under low-serum conditions and anchorage-independent growth. We also found that Zfp296 expression was upregulated in the tumor area of a mouse model of colon carcinogenesis. In addition, the expression levels of ZFP296 in various human cell lines were generally low in normal cells and relatively high in cancer cells. Finally, using a soft agar assay, we found that overexpression of ZFP296 promoted the anchorage-independent growth of cancer cells, while its knockdown had the opposite effect. Overall, these results suggest a possible role of the ES-specific transcription factor ZFP296 in cancer.

癌细胞和胚胎干细胞(ES)具有一些共同的生物学特性,这表明ES细胞中表达的一些基因可能在癌细胞生长过程中发挥重要作用。在这项研究中,我们研究了锌指蛋白296(ZFP296)--一种在ES细胞中表达的转录因子--在癌症发展中可能扮演的角色。首先,我们发现在 NIH3T3 小鼠成纤维细胞中过表达 Zfp296 会诱导两种表明细胞转化的现象:低血清条件下增殖增强和锚定依赖性生长。我们还发现,Zfp296 在结肠癌小鼠模型的肿瘤区表达上调。此外,ZFP296 在各种人类细胞系中的表达水平在正常细胞中普遍较低,而在癌细胞中则相对较高。最后,通过软琼脂试验,我们发现过表达 ZFP296 会促进癌细胞的锚定依赖性生长,而敲除 ZFP296 则会产生相反的效果。总之,这些结果表明,ES特异性转录因子ZFP296可能在癌症中发挥作用。
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引用次数: 0
Polarized contact behavior in directionally migrating Xenopus gastrula mesendoderm. 定向迁移的非洲爪蟾原肠胚中的极化接触行为。
Pub Date : 2023-01-01 DOI: 10.1387/ijdb.230123rw
Martina Nagel, Rudolf Winklbauer

The control of cell-cell adhesion and detachment is essential for collective migration and cell rearrangement. Here, we have used the contact behavior of Xenopus gastrula mesoderm explants migrating directionally on ectoderm conditioned substratum to study the regulation of active cell-cell detachment. When colliding laterally, explants repelled each other, whereas they fused front-to-back when aligned in the direction of migration. For this mesoderm polarization by the substratum, we identified three control modules. First, PDGF-A signaling normally suppresses contact-induced collapse of lamellipodia in a polarized manner. Disruption of PDGF-A function, or of Xwnt6, decreased the polarization of explant contact behavior. Second, the Wnt receptor Xfz7 acted upstream of the kinase Pak1 to control explant fusion independently of PDGF-A-promoted lamellipodia stability. Third, ephrinB1 acted with Dishevelled (Dvl) in front-to-back explant fusion. The second and third modules have been identified previously as regulators of tissue separation at the ectoderm-mesoderm boundary. On non-polarizing, fibronectin-coated substratum, they controlled repulsion between explants in the same way as between tissues during boundary formation. However, explant repulsion/fusion responses were reversed on conditioned substratum by the endogenous guidance cues that also control oriented contact inhibition of lamellipodia. Together, control modules and substratum-bound guidance cues combine preferential front-back adhesion and diminished lateral adhesion of cells to promote collective directional mesoderm migration.

细胞-细胞粘附和分离的控制对于集体迁移和细胞重排至关重要。在这里,我们利用非洲爪蟾原肠胚中胚层外植体在外胚层条件基质上定向迁移的接触行为来研究活性细胞-细胞分离的调控。当横向碰撞时,外植体相互排斥,而当沿着迁移方向排列时,它们前后融合。对于基质引起的中胚层极化,我们确定了三个控制模块。首先,PDGF-A信号传导通常以极化的方式抑制接触诱导的lamellipodia的塌陷。PDGF-A功能或Xwnt6的破坏降低了外植体接触行为的极化。其次,Wnt受体Xfz7在激酶Pak1的上游起作用,独立于PDGF-A驱动的lamellipodia稳定性来控制外植体融合。第三,ephrinB1与Disheveled(Dvl)在外植体前后融合中起作用。第二和第三模块先前已被确定为外胚层-中胚层边界组织分离的调节因子。在非极化的纤连蛋白涂层基质上,它们以与边界形成过程中组织之间相同的方式控制外植体之间的排斥。然而,外植体的排斥/融合反应在条件基质上被内源性引导线索逆转,内源性引导线索也控制着片状足类的定向接触抑制。控制模块和基质结合的指导线索将细胞的优先前后粘附和减少的横向粘附结合在一起,以促进中胚层的集体定向迁移。
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引用次数: 0
Insights into the role of the Wnt signaling pathway in the regeneration of animal model systems. Wnt信号通路在动物模型系统再生中的作用。
Pub Date : 2023-01-01 DOI: 10.1387/ijdb.220144yl
Katarzyna S Walczyńska, Ling Zhu, Yujun Liang

Regeneration enables the regrowth and restoration of missing body parts. It is a common phenomenon among animals. However, only some species exhibit remarkable regeneration capabilities and can regenerate organs such as limbs, lenses or hearts. Regeneration has been widely studied, thereby giving rise to new fields, such as regenerative medicine. Furthermore, regeneration has the potential to be applied to the human body. However, the molecular mechanisms governing this process should be elucidated first. Recent advancements in research methods have led to the identification of numerous signaling pathways involved in regeneration. One of them, the Wnt transduction pathway, is an ancient and evolutionarily conserved pathway that plays an important role in both embryonic development and regeneration. The Wnt pathway plays an important role during the regeneration process, as it is implicated in cell fate determination, cell migration, cell polarity and adult cell homeostasis. To date, two major Wnt pathways have been identified: the canonical (β-catenin dependent) pathway and the non-canonical pathway. The latter pathway can be further divided into planar cell polarity, the Wnt/Ca2+ pathway and the JNK pathway. In this review, we summarize the current state of knowledge regarding the Wnt signaling pathway and its role in regeneration, with a particular emphasis on key model species.

再生可使缺失的身体部位再生和修复。这是动物中常见的现象。然而,只有一些物种表现出非凡的再生能力,能够再生四肢、晶状体或心脏等器官。再生已经被广泛研究,从而产生了新的领域,如再生医学。此外,再生具有应用于人体的潜力。然而,应该首先阐明控制这一过程的分子机制。研究方法的最新进展导致了许多与再生有关的信号通路的鉴定。其中之一,Wnt转导途径,是一种古老且进化保守的途径,在胚胎发育和再生中发挥着重要作用。Wnt途径在再生过程中发挥着重要作用,因为它与细胞命运决定、细胞迁移、细胞极性和成体细胞稳态有关。到目前为止,已经确定了两种主要的Wnt途径:经典(β-连环蛋白依赖)途径和非经典途径。后一种途径可进一步分为平面细胞极性、Wnt/Ca2+途径和JNK途径。在这篇综述中,我们总结了关于Wnt信号通路及其在再生中的作用的知识现状,特别强调了关键的模式物种。
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引用次数: 0
Strontium-doped hydroxyapatite and its role in osteogenesis and angiogenesis 掺锶羟基磷灰石及其在骨生成和血管生成中的作用
Pub Date : 2023-01-01 DOI: 10.1387/ijdb.230091lc
Ling Ran, Lishuang Liu, Jingjing Gao, Yang Pan, Murugan Ramalingam, Xiaoyu Du, Ying Liu, Lijia Cheng, Zheng Shi
For the past 50 years, hydroxyapatite (HA) has been widely used in bone defect repair because it is the main inorganic component of the mineral phase of a human bone. Extensive preclinical and clinical studies have shown that strontium (Sr) can safely and effectively help prevent and treat bone diseases, including osteoporosis. These findings have resulted in the concept of integrating Sr and HA for bone disease management. The doped Sr can improve the physicochemical properties of HA and enhance its angiogenic and bone regeneration ability. Nevertheless, no study has reviewed the design strategy of Sr-doped HA (Sr-HA) to understand its biological roles. Therefore, in this article, we review recent developments in Sr-HA preparation and its effect on osteogenesis and angiogenesis in vitro and in vivo along with key suggestions for future research and development.
羟基磷灰石(hydroxyapatite, HA)作为人体骨骼矿物相的主要无机成分,在近50年来被广泛应用于骨缺损修复。广泛的临床前和临床研究表明,锶(Sr)可以安全有效地帮助预防和治疗包括骨质疏松症在内的骨骼疾病。这些发现产生了将Sr和HA结合起来治疗骨病的概念。掺入锶可以改善透明质酸的理化性质,增强其血管生成和骨再生能力。然而,没有研究回顾了Sr-HA (Sr-HA)的设计策略来了解其生物学作用。因此,本文综述了近年来Sr-HA制备及其在体外和体内成骨和血管生成中的作用,并提出了未来研究和开发的重点建议。
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引用次数: 0
Developmental Biology: from genes to functional organism - news from the 3rd Meeting of the Visegrád Group Society for Developmental Biology. 发育生物学:从基因到功能性生物体--第三届维舍格拉德集团发育生物学学会会议新闻。
Pub Date : 2023-01-01 DOI: 10.1387/ijdb.230228et
Ewelina Trela, Agnieszka Walewska

The third meeting of the Visegrád Group Society for Developmental Biology (V4SDB) was held on September 8th-10th, 2023 in Warsaw, Poland. It was a continuation of previous meetings, the first organized in the Czech Republic in 2018 and the second in Hungary in 2021. Similarly to the previous meetings, the organizers created a friendly platform for networking and science sharing. The conference gathered an excellent group of 160 researchers working on various animal models, who during lecture and poster sessions discussed a broad range of subjects, including early embryonic development, organogenesis, genetic and epigenetic control of developmental processes, stem cells and regeneration, cellular dynamics and migration in developmental biology, and in vitro models in development and disease. Additionally, two satellite events were organized: the Young Developmental Biologists' Forum, which gave young researchers an opportunity to share and promote their work and to participate in hands-on courses, and an outreach initiative "Developmental Biology for Everyone", which presented different aspects of developmental biology to a broad audience.

维舍格拉德集团发育生物学学会(V4SDB)第三次会议于 2023 年 9 月 8 日至 10 日在波兰华沙举行。这是前几次会议的延续,第一次会议于2018年在捷克共和国举行,第二次会议于2021年在匈牙利举行。与前几次会议类似,组织者为网络和科学分享创建了一个友好的平台。本次会议汇聚了 160 名从事各种动物模型研究的优秀研究人员,他们在讲座和海报环节讨论了广泛的主题,包括早期胚胎发育、器官形成、发育过程的遗传和表观遗传控制、干细胞和再生、发育生物学中的细胞动力学和迁移,以及发育和疾病中的体外模型。此外,还组织了两项卫星活动:青年发育生物学家论坛,为青年研究人员提供了分享和推广其工作以及参加实践课程的机会;以及 "人人都可学习的发育生物学 "外联活动,向广大受众介绍发育生物学的不同方面。
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引用次数: 0
Heterogeneity of quiescent and active neural stem cells in the postnatal brain. 出生后大脑中静止和活跃神经干细胞的异质性。
Pub Date : 2022-02-21 DOI: 10.1387/ijdb.220010ik
Dimitrios Dimitrakopoulos, D. Kakogiannis, I. Kazanis
In the postnatal mammalian brain, neurogenic activity is retained in anatomically restricted areas, driven by pools of Neural Stem Cells (NSCs). These cells and their progeny have been studied intensively as potential targets for regenerative treatments, aiming either to their in situmanipulation, or to their use as sources of cells for transplantation-based strategies. Although their full identity, heterogeneity and differentiation potential remain elusive, due to the absence of specific cell-type markers, our knowledge on their properties is constantly expanding. Here, we focus on the NSC niche that is located at the Subependymal Zone (SEZ/ also known as Subventricular Zone) of the lateral ventricles of the brain. We review, summarize and explain the different faces of the NSC, as they have been described using a wide range of experimental approaches in a time-frame of three decades: the primitive, definitive, quiescent or activated NSC. We also review the accumulating evidence on the existence of latent NSCs outside of niches, in the brain parenchyma, that constitute new promising therapeutic targets, complemented by the novel technologies of in vivocell reprogramming.
在出生后的哺乳动物大脑中,神经源性活动保留在解剖学上受限的区域,由神经干细胞(NSCs)池驱动。这些细胞及其后代作为再生治疗的潜在靶点已被深入研究,旨在对其进行情境操作,或将其用作基于移植策略的细胞来源。尽管由于缺乏特定的细胞类型标记物,它们的完整身份、异质性和分化潜力仍然难以捉摸,但我们对它们特性的了解正在不断扩大。在这里,我们关注的是位于脑侧脑室室管膜下区(SEZ/也称为室下区)的NSC生态位。我们回顾、总结和解释了NSC的不同面貌,因为它们已经在三十年的时间框架内使用广泛的实验方法进行了描述:原始的、确定的、静止的或激活的NSC。我们还回顾了越来越多的证据表明,在脑实质中存在潜在的NSCs,它们构成了新的有希望的治疗靶点,并辅以体内细胞重编程的新技术。
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引用次数: 0
Epithelial endothelial transition and endothelial mesenchymal transition.
Pub Date : 2022-02-21 DOI: 10.1387/ijdb.210234dr
D. Ribatti
The movement of continuous sheets of epithelial cells occurs during embryonic development, tissue repair, and cancer. Common to cellular and molecular principles of collective cell migration, invading cancers seem to reactivate embryonic pathways and patterns of cell movement. Epithelial cells possess the capability to become mesenchymal cells in a process called epithelial mesenchymal transition (EMT), which has been extensively studied and described. The aim of this article is to summarizes the most recent literature data concerning less known epithelial-endothelial transition and endothelial-mesenchymal transition.
在胚胎发育、组织修复和癌症过程中,连续的上皮细胞片会发生运动。与细胞集体迁移的细胞和分子原理一样,入侵的癌症似乎重新激活了细胞运动的胚胎途径和模式。上皮细胞在上皮间充质转化(Epithelial mesenchymal transition, EMT)过程中具有成为间充质细胞的能力,这一过程已被广泛研究和描述。本文的目的是总结最近鲜为人知的上皮-内皮转化和内皮-间质转化的文献数据。
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引用次数: 1
Hyaluronan receptor CD44: developmentally regulated expression and role in the early chick embryo. 透明质酸受体CD44:发育调控的表达及其在早期鸡胚中的作用。
Pub Date : 2022-02-21 DOI: 10.1387/ijdb.220008nz
K. Konstantopoulos, Alexandros Dimiropoulos, N. Zagris
CD44 is a membrane glycoprotein and is the main receptor for hyaluronan. We studied the CD44 expression and spatio-temporal distribution by RT-PCR and immunofluorescence, and used an anti-CD44 blocking antibody to perturb CD44-depended signalling programs in the early chick embryo. The intense CD44 levels we detected in the morula embryo (XI) were of novel interest suggestive of a maternally stored transcript. Intriguingly, the CD44 early presence seemed to be essential for the rapid synthesis of hyaluronan. At stage XIII (blastula), CD44 expression was intense in the epiblast and hypoblast. During gastrulation (HH3-4), the cells ingressing into the primitive groove and migrating and the blood islands expressed CD44 intensely. At HH8, the folding neural plate showed polarity regulation of CD44 expression, and expression was also intense in neural crest, notochord, and blood islands. During early organogenesis, CD44 was expressed intensely in the developing cranial and caudal neural tube which showed polarity regulation, in optic stalks, otic vesicles, pre-and migratory neural crest cells, ganglia, notochord, pharynx, gut, liver, aortae, heart, somites, vascular area, amnion, chorion and was distinct in extracellular matrix of cranial neural tube and otic vesicle lumens. Antibody-mediated perturbation of CD44 function resulted in unorganized extracellular matrix, loss of tissue spaces, grossly abnormal notochord, intermingling of clumped neuroectoderm and mesenchyme, absence of somites and blood vessels, inhibition of neural crest cell emigration. CD44 has various pivotal roles in matrix integrity and tissue patterning consistent with its known biochemical features and interactions with hyaluronan, growth factors, receptors and other signaling molecules.
CD44是一种膜糖蛋白,是透明质酸的主要受体。我们利用RT-PCR和免疫荧光技术研究了CD44的表达和时空分布,并利用抗CD44阻断抗体干扰早期鸡胚中CD44依赖的信号程序。有趣的是,CD44的早期存在似乎对透明质酸的快速合成至关重要。在第XIII期(囊胚),CD44在外胚层和下胚层表达强烈。在原肠胚形成(HH3-4)过程中,细胞进入原始沟槽迁移和血岛强烈表达CD44。在HH8时,折叠神经板显示CD44的极性表达调控,神经嵴、脊索和血岛的表达也很强烈。在器官发生早期,CD44在发育中的具有极性调节的颅神经管、尾神经管、视柄、耳小泡、前移和迁移的神经嵴细胞、神经节、脊索、咽、肠、肝、主动脉、心脏、体、血管区、羊膜、绒毛膜中表达强烈,在颅神经管和耳小泡管腔的细胞外基质中表达明显。抗体介导的CD44功能的扰动导致细胞外基质无组织,组织间隙丧失,脊索严重异常,神经外胚层和间质团块混杂,体和血管缺失,神经嵴细胞迁移抑制。CD44在基质完整性和组织模式中具有多种关键作用,这与它已知的生化特征和与透明质酸、生长因子、受体和其他信号分子的相互作用一致。
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引用次数: 0
Pleiotrophin, nitric oxide and glutamate AMPA receptors in chick cerebellum morphogenesis. 鸡小脑形态发生中的多养蛋白、一氧化氮和谷氨酸AMPA受体。
Pub Date : 2022-02-09 DOI: 10.1387/ijdb.210213cd
Vasiliki Kommata, Evaggelia Alexopoulou, Elentina K. Argyrousi, C. Dermon
Avian cerebellum, a highly conserved, laminated and foliated structure, provides an excellent model for developmental studies. During the intermediate embryonic stages, granule cell progenitor proliferation and the inwards migration of post-mitotic granule cells have been implicated in the morphogenesis of cerebellar cortex cytoarchitecture and foliation. The present study questioned the spatio-temporal expression pattern of pleiotrophin, an extracellular matrix growth factor, during the morphogenesis of embryonic cerebellum and the roles of ionotropic AMPA glutamate receptors and the diffusible neuromodulator nitric oxide (NO) in the proliferation pattern of EGL granule cell progenitors. For this, the density of proliferating cells in the developing embryonic external granule layer (EGL) was determined following acute treatment with AMPA receptor antagonist CNQX or NO synthase inhibitor L-NAME, at embryonic stages HH38-41 (E12-E15 days), by means of BrdU immunohistochemistry and double immunofluorescence. Importantly, at earlier stages pleiotrophin-like immunoreactivity showed high expression levels in the EGL that gradually decreased, persisting within the growing folia apices, later in development. Interestingly, blockage of AMPA receptors had no effect; while NOS inhibition resulted in transient age- and region-specific increases of EGL granule progenitor cell proliferation at earlier stages, but decreased the post-mitotic granule cells at folia apices, at a later stage HH41 (E15 day). Taken all together, NO had a transient anti-proliferative effect in EGL similar to mammalian cerebellum, acting as a modulator of the EGL function at different stages, suggesting its possible implication in complex processes guiding cerebellar cytoarchitecture and folia formation.
鸟类小脑是一种高度保守的层状和叶状结构,为发育研究提供了一个很好的模型。在胚胎中期,颗粒细胞祖细胞的增殖和有丝分裂后颗粒细胞的向内迁移与小脑皮层的细胞结构和叶状结构的形态发生有关。本研究探讨了细胞外基质生长因子多营养因子在胚胎小脑形态发生过程中的时空表达模式,以及嗜离子性AMPA谷氨酸受体和扩散性神经调节剂一氧化氮(NO)在EGL颗粒细胞祖细胞增殖过程中的作用。为此,在胚胎期HH38-41 (E12-E15天),用AMPA受体拮抗剂CNQX或NO合酶抑制剂L-NAME急性治疗后,采用BrdU免疫组织化学和双免疫荧光法测定发育中的胚胎外颗粒层(EGL)增殖细胞密度。重要的是,在早期阶段,多营养因子样免疫反应性在EGL中表现出高表达水平,并逐渐降低,在发育后期持续存在于生长的叶尖中。有趣的是,阻断AMPA受体没有影响;在HH41晚期(E15天),NOS抑制作用导致EGL颗粒祖细胞增殖在早期短暂的年龄特异性和区域特异性增加,但在叶尖有丝分裂后颗粒细胞增殖减少。综上所述,NO在EGL中具有类似于哺乳动物小脑的短暂抗增殖作用,在不同阶段作为EGL功能的调节剂,提示其可能参与指导小脑细胞结构和叶叶形成的复杂过程。
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引用次数: 0
期刊
The International journal of developmental biology
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