embryogenesis

胚胎发生
  • 文章类型: Journal Article
    通过应激颗粒的组装来控制整体蛋白质合成代表了真核细胞面对各种应激条件所采用的策略。TIA1相关核溶素(TIAR),曲司曲普林(TTP),Ras-GTP酶激活蛋白SH3结构域结合蛋白(G3BP)是应激颗粒的关键成分,允许调节mRNA的稳定性,从而不仅控制应激反应,而且控制细胞增殖和分化。在这项研究中,我们的目的是调查蒂尔的角色,ttp,在生理和胁迫条件下,孤立海鞘Cionarobusta的胚胎发育过程中和g3bp。我们进行了CRISPR/Cas9来评估基因敲除对正常胚胎发育的影响。和基因报告基因测定来研究基因转录的时间和组织特异性,以及全装原位杂交和定量实时PCR。诱发急性应激状态,我们使用铁和镉作为“必需”和“非必需”金属,分别。我们的结果强调,第一次,提尔的重要性,ttp,和g3bp在无脊椎动物脊索动物胚胎发育过程中控制中内胚层组织衍生物的发育。
    Controlling global protein synthesis through the assembly of stress granules represents a strategy adopted by eukaryotic cells to face various stress conditions. TIA 1-related nucleolysin (TIAR), tristetraprolin (TTP), and Ras-GTPase-activating protein SH3-domain-binding protein (G3BP) are key components of stress granules, allowing the regulation of mRNA stability, and thus controlling not only stress responses but also cell proliferation and differentiation. In this study, we aimed at investigating the roles of tiar, ttp, and g3bp during embryogenesis of the solitary ascidian Ciona robusta under both physiological and stress conditions. We carried out CRISPR/Cas9 to evaluate the effects of gene knockout on normal embryonic development, and gene reporter assay to study the time and tissue specificity of gene transcription, together with whole-mount in situ hybridization and quantitative real time PCR. To induce acute stress conditions, we used iron and cadmium as \"essential\" and \"non-essential\" metals, respectively. Our results highlight, for the first time, the importance of tiar, ttp, and g3bp in controlling the development of mesendodermal tissue derivatives during embryogenesis of an invertebrate chordate.
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  • 文章类型: Journal Article
    基底细胞癌(BCC)是一种独特的肿瘤,由于其独特的组织学特征和临床行为,例如上皮和基质的持续二元参与,实际上没有转移,并且有特定的解剖部位发生和传播。长期以来,人们一直假设BCC的发作与发育异常过程之间存在潜在的相关性。对支持该理论的PubMed索引出版物的选择性调查检索了1901年至2024年之间发表的64篇精选文章。从我们的文献综述分析来看,确定了BCC胚胎发育异常发病机制的五个主要研究领域:(1)BCC的地形分布与宏观胚胎学之间的相关性,(2)BCC与显微胚胎学的相关性,(3)遗传性BCC,(4)BCC与毛囊的相干性和(5)BCC与份子胚胎学的相干性具有特异性的聚焦Hedgehog旌旗灯号通路。来自微观和分子研究的大量数据一致支持BCC发生异常发病机理的假设。这些证据正在促进这种疾病的临床管理的进步,正在开发基于免疫调节的创新靶向分子疗法。
    The Basal Cell Carcinoma (BCC) is a sort of unique tumour due to its combined peculiar histological features and clinical behaviour, such as the constant binary involvement of the epithelium and the stroma, the virtual absence of metastases and the predilection of specific anatomical sites for both onset and spread. A potential correlation between the onset of BCC and a dysembryogenetic process has long been hypothesised. A selective investigation of PubMed-indexed publications supporting this theory retrieved 64 selected articles published between 1901 and 2024. From our analysis of the literature review, five main research domains on the dysembryogenetic pathogenesis of BCC were identified: (1) The correlation between the topographic distribution of BCC and the macroscopic embryology, (2) the correlation between BCC and the microscopic embryology, (3) the genetic BCC, (4) the correlation between BCC and the hair follicle and (5) the correlation between BCC and the molecular embryology with a specific focus on the Hedgehog signalling pathway. A large amount of data from microscopic and molecular research consistently supports the hypothesis of a dysembryogenetic pathogenesis of BCC. Such evidence is promoting advances in the clinical management of this disease, with innovative targeted molecular therapies on an immune modulating basis being developed.
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  • 文章类型: Journal Article
    人类生育能力欠佳,部分原因是在早期分裂阶段容易出错,导致非整倍性。大多数人类植入前是整倍体和非整倍体细胞的镶嵌,然而,非整倍体细胞比例较低的镶嵌胚胎与完全整倍体胚胎发育到足月的可能性相似。胚胎在发育过程中如何管理非整倍性还知之甚少。这些知识对于改善生育治疗和减少发育缺陷至关重要。为了探索这些机制,我们建立了一种新的小鼠染色体镶嵌模型,以研究非整倍体细胞在植入前发育过程中的命运。我们以前使用Mps1抑制剂reversine在胚胎中产生非整倍性。这里,我们发现,用更特异性的Mps1抑制剂AZ3146治疗可诱导植入前胚胎的染色体分离缺陷,类似于逆转。然而,AZ3146处理的胚胎显示出比逆转处理的胚胎更高的发育潜力。与逆转处理的胚胎不同,AZ3146处理的胚胎表现出缺氧诱导因子-1A(HIF1A)的瞬时上调,并且缺乏p53上调。植入前胚胎在体内低氧环境中发育,和体外低氧暴露减少了响应Mps1抑制的DNA损伤,并增加了镶嵌上胚层中整倍体细胞的比例。在镶嵌胚中抑制HIF1A也降低了镶嵌胚中非整倍体细胞的比例。我们的工作阐明了提高镶嵌胚胎发育潜力的潜在策略。
    Human fertility is suboptimal, partly due to error-prone divisions in early cleavage-stages that result in aneuploidy. Most human pre-implantation are mosaics of euploid and aneuploid cells, however, mosaic embryos with a low proportion of aneuploid cells have a similar likelihood of developing to term as fully euploid embryos. How embryos manage aneuploidy during development is poorly understood. This knowledge is crucial for improving fertility treatments and reducing developmental defects. To explore these mechanisms, we established a new mouse model of chromosome mosaicism to study the fate of aneuploid cells during pre-implantation development. We previously used the Mps1 inhibitor reversine to generate aneuploidy in embryos. Here, we found that treatment with the more specific Mps1 inhibitor AZ3146 induced chromosome segregation defects in pre-implantation embryos, similar to reversine. However, AZ3146-treated embryos showed a higher developmental potential than reversine-treated embryos. Unlike reversine-treated embryos, AZ3146-treated embryos exhibited transient upregulation of Hypoxia Inducible-Factor-1A (HIF1A) and lacked p53 upregulation. Pre-implantation embryos develop in a hypoxic environment in vivo, and hypoxia exposure in vitro reduced DNA damage in response to Mps1 inhibition and increased the proportion of euploid cells in the mosaic epiblast. Inhibiting HIF1A in mosaic embryos also decreased the proportion of aneuploid cells in mosaic embryos. Our work illuminates potential strategies to improve the developmental potential of mosaic embryos.
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  • 文章类型: Journal Article
    连体双胞胎是哺乳动物中罕见的先天性畸形。本研究提出了两种不同的情况。案件编号1个特征单头,Pietrain品种的胸椎-连体双胎仔猪,和案件编号2个特征单头,胸椎连体成对的双生仔猪,具有股裂和双裂根舌的混合品种。使用验尸和计算机断层扫描(CT)检查对这些病例进行了检查。在这两种情况下,连体对称双胞胎只有一个头,一个脖子,和融合的胸腔,而腹腔被分离。同样,在这两种情况下,他们有四个前肢和四个后肢和重复的大孔。CT检查时,以防没有。1,在颅骨和脊柱中观察到严重的异常。在左边的双胞胎中,从C2椎骨直到脊柱末端都可以看到隐匿性发育不良,在右边的双胞胎中,从C3椎骨直到状态椎骨水平结束。以防没有。如图2所示,口腔包含一个舌头,该舌头具有与一个舌骨相连的双裂根。软腭出现了一个小裂口。CT检查时,顶骨和枕骨部分复制。这个案例还表现出隐匿性的神秘主义,但仅限于颈椎,C1-C6为左双胞胎,C1-C5为右双胞胎。在这两种情况下,尸检期间发现内脏器官异常。这里提出的具有多种先天性异常的连体双胞胎增强了我们对兽医学中连体病例的各种临床形式的理解。
    Conjoined twins are rare congenital malformations that have been reported in mammals. Two different cases are presented in this study. Case No. 1 features monocephalic, thoracopagus-conjoined twin piglets with anencephaly and palatoschisis of the Pietrain breed, and case No. 2 features monocephalic, thoracopagus conjoined twin piglets with palatoschisis and bifid root tongue of a mixed breed. These cases were examined using post-mortem and computed tomography (CT) examinations. In both cases, the conjoined symmetrical twins had a single head, one neck, and fused thoracic cavities, while the abdominal cavities were separated. Similarly, in both cases, they had four forelimbs and four hindlimbs and duplicated foramen magnum. During CT examination, in case No. 1, severe abnormalities were observed in the skull and vertebral column. In the left twin, occult dysraphism was seen from the C2 vertebra until the end of the vertebral column, and in the right twin, from the C3 vertebra until the end of the state vertebral level. In case No. 2, the oral cavity contained a tongue with a bifid root connected with one hyoid bone, and the soft palate presented a small cleft. During CT examination, the parietal bone and the occipital bones were partially duplicated. This case also presented occult dysraphism, but only in the cervical vertebrae, C1-C6 for the left twin and C1-C5 for the right twin. In both cases, abnormalities of the internal organs were revealed during necropsy. Conjoined twins with multiple congenital anomalies presented here enhance our understanding of the various clinical forms of conjoined cases in veterinary medicine.
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  • 文章类型: Journal Article
    微管动力学的调节在关键的发育转变过程中至关重要,例如配子发生,受精,胚胎发生,和种子形成,细胞在形状和功能上经历快速变化。在植物中,katanin在微管动力学中起着至关重要的作用。本研究调查了拟南芥中的两个种子发育突变体,命名为elk5-1D(类直立5,ELK5)和loo1(棒棒糖1),以圆形种子为特征,侏儒症,和生育缺陷。值得注意的是,elk5-1D表现出显性遗传模式,而loo1是隐性的。通过位置克隆,我们将这两个突变体鉴定为KATANIN1(KTN1)基因的新等位基因,它编码一种对细胞分裂和形态至关重要的微管切断酶。KTN1中的突变破坏胚胎细胞分裂并导致双胚胎表型的出现。我们的发现强调了KTN1在生育力和早期胚胎发育中的重要作用。可能影响生殖细胞的命运。
    Regulation of microtubule dynamics is crucial during key developmental transitions such as gametogenesis, fertilization, embryogenesis, and seed formation, where cells undergo rapid changes in shape and function. In plants, katanin plays an essential role in microtubule dynamics. This study investigates two seed developmental mutants in Arabidopsis thaliana, named elk5-1D (erecta-like 5, ELK5) and loo1 (lollipop 1), which are characterized by round seeds, dwarfism, and fertility defects. Notably, elk5-1D exhibits a dominant inheritance pattern, whereas loo1 is recessive. Through positional cloning, we identified both mutants as new alleles of the KATANIN 1 (KTN1) gene, which encodes a microtubule-severing enzyme critical for cell division and morphology. Mutations in KTN1 disrupt embryo cell division and lead to the emergence of a twin embryo phenotype. Our findings underscore the essential role of KTN1 in fertility and early embryonic development, potentially influencing the fate of reproductive cells.
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  • 文章类型: Journal Article
    R-loop,染色质结构包含一个RNA:DNA杂交体和一个未配对的单链DNA,发挥多种生物学作用。然而,由于技术限制,胚胎发育过程中R环的景观和潜在功能仍然难以捉摸。这里,我们开发了一种定量和高分辨率的超低输入R环分析方法,命名为ULI-ssDRIP-seq,它可以映射全球R循环与1000个细胞。通过使用ULI-ssDRIP-seq,我们揭示了斑马鱼从配子到早期胚胎的R环动态。在卵母细胞中,在核基因组的大多数区域,R环水平相对较低,除了母系遗传的rDNA和线粒体基因组。早期发育过程中R-loop和CG甲基化动力学之间的相关性相对较弱。此外,通过敲低或过表达RNaseH1来上调或下调全局R环,会导致胚胎发育延迟,合子和母本基因的表达发生巨大变化。这项研究提供了早期脊椎动物胚胎发生过程中全面的R环景观,并证明了R环在胚胎发育中的意义。
    R-loop, a chromatin structure containing one RNA:DNA hybrid and one unpaired single-stranded DNA, plays multiple biological roles. However, due to technical limitations, the landscapes and potential functions of R-loops during embryogenesis remain elusive. Here, we developed a quantitative and high-resolution ultra-low input R-loop profiling method, named ULI-ssDRIP-seq, which can map global R-loops with as few as 1000 cells. By using ULI-ssDRIP-seq, we reveal the R-loop dynamics in the zebrafish from gametes to early embryos. In oocytes, the R-loop level is relatively low in most regions of the nuclear genome, except maternal-inherited rDNA and mitochondrial genome. The correlation between R-loop and CG methylation dynamics during early development is relatively weak. Furthermore, either up- or down-regulation of global R-loops by knockdown or overexpression of RNase H1 causes a delay of embryonic development with dramatic expression changes in zygotic and maternal genes. This study provides comprehensive R-loop landscapes during early vertebrate embryogenesis and demonstrates the implication of R-loops in embryonic development.
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  • 文章类型: Journal Article
    由其膜定义的细胞的形状可以与其生理状态密切相关。例如,癌细胞的不规则形状和神经元细胞的细长形状通常反映特定的功能,如细胞运动和细胞通讯。然而,目前尚不清楚细胞形状描述符是否以及哪种细胞形状描述符可以表征不同的细胞生理状态。在这项研究中,从先前的文献中收集三维(3D)对象的12个几何形状描述符,并用基于秀丽隐杆线虫胚胎中细胞膜的荧光标记分割的~400,000个独立3D细胞区域的公共数据集进行测试。揭示了这些形状描述符可以忠实地表征细胞生理状态,包括(1)细胞分裂(胞质分裂),随着伸长率的突然增加;(2)细胞迁移速度与细胞球形度呈负相关;(3)细胞谱系规范与对称图案化的细胞形状变化;(4)细胞命运规范与差异基因表达和差异细胞形状。建立的描述符可用于识别和预测许多细胞中的不同生理状态。它不仅可用于研究发育形态发生,还可用于诊断人类疾病(例如,异常细胞的快速检测)。
    The shape of a cell as defined by its membrane can be closely associated with its physiological state. For example, the irregular shapes of cancerous cells and elongated shapes of neuron cells often reflect specific functions, such as cell motility and cell communication. However, it remains unclear whether and which cell shape descriptors can characterize different cellular physiological states. In this study, 12 geometric shape descriptors for a three-dimensional (3D) object were collected from the previous literature and tested with a public dataset of ~400,000 independent 3D cell regions segmented based on fluorescent labeling of the cell membranes in Caenorhabditis elegans embryos. It is revealed that those shape descriptors can faithfully characterize cellular physiological states, including (1) cell division (cytokinesis), along with an abrupt increase in the elongation ratio; (2) a negative correlation of cell migration speed with cell sphericity; (3) cell lineage specification with symmetrically patterned cell shape changes; and (4) cell fate specification with differential gene expression and differential cell shapes. The descriptors established may be used to identify and predict the diverse physiological states in numerous cells, which could be used for not only studying developmental morphogenesis but also diagnosing human disease (e.g., the rapid detection of abnormal cells).
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  • 文章类型: Journal Article
    头足类动物和脊椎动物的最后一个共同祖先生活在大约5.8亿年前,然而胚状体头足类动物,包括鱿鱼,乌贼和章鱼,已经发展出一种非凡的行为方式,包括学习行为和工具利用。这些动物还开发了创新的先进防御机制,例如伪装和墨水释放。它们进化出独特的生命周期,拥有最大的无脊椎动物神经系统。因此,研究coleoid头足类动物提供了一个独特的机会,可以深入了解大型集中神经系统的进化和发展。作为非模型物种,分子和遗传工具仍然有限。然而,已经获得了对胚胎大脑发育进行反卷积的重要见解。即使胚状体头足类动物的中枢神经系统具有典型的软体动物环食管bauplan,它的发展方面让人想起在脊椎动物中观察到的过程,如远距离神经元迁移。这篇综述概述了胚胎类头足类研究,重点是神经发生的细胞和分子方面。迁移和图案。此外,我们总结了最近关于胚胎和孵化头足类大脑中神经细胞类型多样性的工作。最后,我们强调了我们知识和未来研究路线的差距。
    The last common ancestor of cephalopods and vertebrates lived about 580 million years ago, yet coleoid cephalopods, comprising squid, cuttlefish and octopus, have evolved an extraordinary behavioural repertoire that includes learned behaviour and tool utilization. These animals also developed innovative advanced defence mechanisms such as camouflage and ink release. They have evolved unique life cycles and possess the largest invertebrate nervous systems. Thus, studying coleoid cephalopods provides a unique opportunity to gain insights into the evolution and development of large centralised nervous systems. As non-model species, molecular and genetic tools are still limited. However, significant insights have already been gained to deconvolve embryonic brain development. Even though coleoid cephalopods possess a typical molluscan circumesophageal bauplan for their central nervous system, aspects of its development are reminiscent of processes observed in vertebrates as well, such as long-distance neuronal migration. This review provides an overview of embryonic coleoid cephalopod research focusing on the cellular and molecular aspects of neurogenesis, migration and patterning. Additionally, we summarize recent work on neural cell type diversity in embryonic and hatchling cephalopod brains. We conclude by highlighting gaps in our knowledge and routes for future research.
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  • 文章类型: Journal Article
    复杂植物结构的产生取决于控制组织细胞生长的不同分子调控网络之间的相互作用,最终塑造每个结构的最终形态特征。组织生长和整体植物形状的调节网络由转录调节因子的复杂网组成,这些转录调节因子协同或竞争以调节下游靶标的表达。转录调控与植物激素网络密切相关,因为转录因子(TF)可能充当激素信号通路的效应子或调节剂。进一步增强分子网络在塑造植物结构方面的能力和灵活性。这里,我们专注于同源域-亮氨酸拉链(HD-ZIP)蛋白,一类植物特异性转录调节因子,并在不同的发育环境中回顾它们与荷尔蒙网络的分子联系。我们讨论了HD-ZIP蛋白如何成为植物激素作用的关键调节剂,并进一步强调了HD-ZIP/激素网络在控制身体计划和植物生长中的基本作用。
    The generation of complex plant architectures depends on the interactions among different molecular regulatory networks that control the growth of cells within tissues, ultimately shaping the final morphological features of each structure. The regulatory networks underlying tissue growth and overall plant shapes are composed of intricate webs of transcriptional regulators which synergize or compete to regulate the expression of downstream targets. Transcriptional regulation is intimately linked to phytohormone networks as transcription factors (TFs) might act as effectors or regulators of hormone signaling pathways, further enhancing the capacity and flexibility of molecular networks in shaping plant architectures. Here, we focus on homeodomain-leucine zipper (HD-ZIP) proteins, a class of plant-specific transcriptional regulators, and review their molecular connections with hormonal networks in different developmental contexts. We discuss how HD-ZIP proteins emerge as key regulators of hormone action in plants and further highlight the fundamental role that HD-ZIP/hormone networks play in the control of the body plan and plant growth.
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  • 文章类型: Journal Article
    植物依赖于干细胞的分裂来建立生长所需的细胞系。在胚胎发生期间,早期分裂产物被认为是干细胞,而在胚胎后发育过程中,干细胞存在于根和芽尖的分生组织中。PLETHORA/AINTEGUMENTA样(PLT/AIL)转录因子是胚胎后分生组织功能的调节因子,是维持干细胞库所必需的。尽管胚胎干细胞和胚胎后干细胞有相似之处,PLT在早期胚胎发生过程中的作用尚未得到彻底研究。这里,我们证明了受精卵中的PLT调节组,顶端和基底细胞与胚胎后分生组织细胞高度一致。我们透露,在所有六个PLT中,只有PLT2和PLT4/BABYBOOM(BBM)在受精卵中表达,这两个因素对于超过合子阶段和第一次分裂的胚胎发生进程至关重要。最后,我们表明,当从PLT2和BBM启动子表达时,其他PLT可以挽救plt2bbm缺陷,建立上游调控作为早期胚胎发生的关键因素。我们的数据表明,通用PLT因子通过诱导分生组织潜能促进拟南芥的早期胚胎发育。
    Plants are dependent on divisions of stem cells to establish cell lineages required for growth. During embryogenesis, early division products are considered to be stem cells, whereas during post-embryonic development, stem cells are present in meristems at the root and shoot apex. PLETHORA/AINTEGUMENTA-LIKE (PLT/AIL) transcription factors are regulators of post-embryonic meristem function and are required to maintain stem cell pools. Despite the parallels between embryonic and post-embryonic stem cells, the role of PLTs during early embryogenesis has not been thoroughly investigated. Here, we demonstrate that the PLT regulome in the zygote, and apical and basal cells is in strong congruence with that of post-embryonic meristematic cells. We reveal that out of all six PLTs, only PLT2 and PLT4/BABY BOOM (BBM) are expressed in the zygote, and that these two factors are essential for progression of embryogenesis beyond the zygote stage and first divisions. Finally, we show that other PLTs can rescue plt2 bbm defects when expressed from the PLT2 and BBM promoters, establishing upstream regulation as a key factor in early embryogenesis. Our data indicate that generic PLT factors facilitate early embryo development in Arabidopsis by induction of meristematic potential.
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