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The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology最新文献

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Morphomolecular neuronal phenotypes in the neocortex reflect phylogenetic relationships among certain mammalian orders. 新皮层的形态分子神经元表型反映了某些哺乳动物目之间的系统发育关系。
Patrick R Hof, Chet C Sherwood

The cytoarchitecture of the cerebral cortex in mammals has been traditionally investigated using Nissl, Golgi, or myelin stains and there are few comparative studies on the relationships between neuronal morphology and neurochemical specialization. Most available studies on neuronal subtypes identified by their molecular and morphologic characteristics have been performed in species commonly used in laboratory research such as the rat, mouse, cat, and macaque monkey, as well as in autopsic human brain specimens. A number of cellular markers, such as neurotransmitters, structural proteins, and calcium-buffering proteins, display a highly specific distribution in distinct classes of neocortical neurons in a large number of mammalian species. In this article, we present an overview of the morphologic characteristics and distribution of three calcium-binding proteins, parvalbumin, calbindin, and calretinin, and of a component of the neuronal cytoskeleton, nonphosphorylated neurofilament protein in the neocortex of various species, representative of the major subdivisions of mammals. The distribution of these neurochemical markers defined several species- and order-specific patterns that permit assessment of the degree to which neuronal morphomolecular specialization, as well as the regional and laminar distribution of distinct cell types in the neocortex, represents derived or ancestral features. In spite of the remarkable diversity in morphologic and cellular organization that occurred during mammalian neocortical evolution, such patterns identified several associations among taxa that closely match their phylogenetic relationships.

哺乳动物大脑皮层的细胞结构传统上是用尼氏染色、高尔基染色或髓磷脂染色来研究的,很少有关于神经元形态和神经化学特化之间关系的比较研究。大多数通过分子和形态特征确定的神经元亚型的现有研究都是在实验室研究中常用的物种中进行的,如大鼠、小鼠、猫和猕猴,以及尸检的人类大脑标本。许多细胞标记物,如神经递质、结构蛋白和钙缓冲蛋白,在许多哺乳动物物种的不同类别的新皮层神经元中显示出高度特异性的分布。在这篇文章中,我们概述了三种钙结合蛋白的形态特征和分布,小白蛋白、钙结合蛋白和钙钙蛋白,以及神经元细胞骨架的一个组成部分,在不同物种的新皮层中,非磷酸化的神经丝蛋白,代表了哺乳动物的主要分支。这些神经化学标记物的分布定义了几种物种和目特异性模式,可以评估神经元形态分子特化的程度,以及新皮层中不同细胞类型的区域和层流分布,代表了衍生或祖先的特征。尽管在哺乳动物新皮层进化过程中,形态和细胞组织存在显著的多样性,但这种模式确定了类群之间的几种联系,这些联系与它们的系统发育关系密切相关。
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引用次数: 55
Anatomical analysis of an aye-aye brain (Daubentonia madagascariensis, primates: Prosimii) combining histology, structural magnetic resonance imaging, and diffusion-tensor imaging. 结合组织学、结构磁共振成像和弥散张量成像对一只猕猴脑的解剖分析(Daubentonia madagascar,灵长类:Prosimii)。
Jason A Kaufman, Eric T Ahrens, David H Laidlaw, Song Zhang, John M Allman

This report presents initial results of a multimodal analysis of tissue volume and microstructure in the brain of an aye-aye (Daubentonia madagascariensis). The left hemisphere of an aye-aye brain was scanned using T2-weighted structural magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) prior to histological processing and staining for Nissl substance and myelinated fibers. The objectives of the experiment were to estimate the volume of gross brain regions for comparison with published data on other prosimians and to validate DTI data on fiber anisotropy with histological measurements of fiber spread. Measurements of brain structure volumes in the specimen are consistent with those reported in the literature: the aye-aye has a very large brain for its body size, a reduced volume of visual structures (V1 and LGN), and an increased volume of the olfactory lobe. This trade-off between visual and olfactory reliance is likely a reflection of the nocturnal extractive foraging behavior practiced by Daubentonia. Additionally, frontal cortex volume is large in the aye-aye, a feature that may also be related to its complex foraging behavior and sensorimotor demands. Analysis of DTI data in the anterior cingulum bundle demonstrates a strong correlation between fiber spread as measured from histological sections and fiber spread as measured from DTI. These results represent the first quantitative comparison of DTI data and fiber-stained histology in the brain.

本报告介绍了一种猕猴桃(Daubentonia madagascar)大脑组织体积和微观结构的多模态分析的初步结果。采用t2加权结构磁共振成像(MRI)和弥散张量成像(DTI)扫描左脑,然后进行组织学处理和尼氏物质和髓鞘纤维染色。该实验的目的是估计脑总区域的体积,以便与其他原脑动物的已发表数据进行比较,并通过纤维扩散的组织学测量来验证DTI关于纤维各向异性的数据。样本中大脑结构体积的测量结果与文献报道的一致:眼猴的大脑体积相对于其体型来说非常大,视觉结构(V1和LGN)的体积减少,而嗅叶的体积增加。这种视觉和嗅觉依赖之间的权衡很可能是Daubentonia夜间采掘觅食行为的反映。此外,在aye-aye时,额叶皮质体积很大,这一特征也可能与其复杂的觅食行为和感觉运动需求有关。对前扣带束DTI数据的分析表明,从组织学切片测量的纤维扩散与从DTI测量的纤维扩散之间存在很强的相关性。这些结果代表了DTI数据和大脑纤维染色组织学的首次定量比较。
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引用次数: 59
Diversity of mammalian photoreceptor properties: adaptations to habitat and lifestyle? 哺乳动物光感受器特性的多样性:对栖息地和生活方式的适应?
Leo Peichl

All mammalian retinae contain rod photoreceptors for low-light vision and cone photoreceptors for daylight and color vision. Most nonprimate mammals have dichromatic color vision based on two cone types with spectrally different visual pigments: a short-wavelength-sensitive (S-)cone and a long-wavelength-sensitive (L-)cone. Superimposed on this basic similarity, there are remarkable differences between species. This article reviews some striking examples. The density ratio of cones to rods ranges from 1:200 in the most nocturnal to 20:1 in a few diurnal species. In some species, the proportion of the spectral cone types and their distribution across the retina deviate from the pattern found in most mammals, including a complete absence of S-cones. Depending on species, the spectral sensitivity of the L-cone pigment may peak in the green, yellow, or orange, and that of the S-cone pigment in the blue, violet, or near-ultraviolet. While exclusive expression of one pigment per cone is the rule, some species feature coexpression of the L- and S-pigment in a significant proportion of their cones. It is widely assumed that all these variations represent adaptations to specific visual needs associated with particular habitats and lifestyles. However, in many cases we have not yet identified the adaptive value of a given photoreceptor arrangement. Comparative anatomy is a fruitful approach to explore the range of possible arrangements within the blueprint of the mammalian retina and to identify species with particularly interesting or puzzling patterns that deserve further scrutiny with physiological and behavioral assays.

所有哺乳动物的视网膜都含有用于弱光视觉的杆状光感受器和用于日光和彩色视觉的锥状光感受器。大多数非灵长类哺乳动物具有基于两种视锥类型的二色视觉,这些视锥类型具有光谱上不同的视觉色素:短波长敏感(S-)视锥和长波长的敏感(L-)视锥。除了这种基本的相似性之外,物种之间还存在着显著的差异。本文回顾了一些引人注目的例子。球果与杆状体的密度比在最夜间为1:200,在少数日间物种中为20:1。在某些物种中,光谱锥型的比例及其在视网膜上的分布与大多数哺乳动物的模式不同,包括完全没有s锥。根据不同的物种,l -锥色素的光谱灵敏度可能在绿色、黄色或橙色达到峰值,而s -锥色素的光谱灵敏度可能在蓝色、紫色或近紫外线达到峰值。虽然每个球果只表达一种色素是规律,但有些物种的球果中L-和s -色素的共表达占很大比例。人们普遍认为,所有这些变化都是对与特定栖息地和生活方式有关的特定视觉需求的适应。然而,在许多情况下,我们还没有确定一个给定的光感受器排列的自适应价值。比较解剖学是一种富有成效的方法,可以探索哺乳动物视网膜蓝图中可能的排列范围,并识别具有特别有趣或令人费解的模式的物种,这些模式值得通过生理和行为分析进一步仔细研究。
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引用次数: 331
Comparative anatomy of the facial motor nucleus in mammals, with an analysis of neuron numbers in primates. 哺乳动物面部运动核的比较解剖学,以及灵长类动物神经元数量的分析。
Chet C Sherwood

The facial motor nucleus (VII) contains motoneurons that innervate the facial muscles of expression. In this review, the comparative anatomy of this brainstem nucleus is examined. Several aspects of the anatomical organization of the VII appear to be common across mammals, such as the distribution of neuron types, general topography of muscle representation, and afferent connections from the midbrain and brainstem. Phylogenetic specializations are apparent in the proportion of neurons allocated to the representation of subsets of muscles and the degree of differentiation among subnuclei. These interspecific differences may be related to the elaboration of certain facial muscles in the context of socioecological adaptations such as whisking behavior, sound localization, vocalization, and facial expression. Furthermore, current evidence indicates that direct descending corticomotoneuron projections in the VII are present only in catarrhine primates, suggesting that this connectivity is an important substrate for the evolution of enhanced mobility and flexibility in facial expression. Data are also presented from a stereologic analysis of VII neuron numbers in 18 primate species and a scandentian. Using phylogenetic comparative statistics, it is shown that there is not a correlation between group size and VII neuron number (adjusted for medulla volume) among primates. Great apes and humans, however, display moderately more VII neurons that expected for their medulla size.

面部运动核(VII)包含支配面部表情肌肉的运动神经元。在这篇综述中,比较解剖的脑干核进行了检查。在哺乳动物中,VII的解剖组织的几个方面似乎是共同的,例如神经元类型的分布,肌肉表征的总体地形,以及中脑和脑干的传入连接。系统发育特化在分配给肌肉亚群的神经元的比例和亚核之间的分化程度上是明显的。这些种间差异可能与某些面部肌肉在社会生态适应背景下的精细程度有关,如轻拂行为、声音定位、发声和面部表情。此外,目前的证据表明,仅在卡他鼻灵长类动物中才存在直接下行的皮质神经元投射,这表明这种连通性是面部表情增强的机动性和灵活性进化的重要基础。我们还对18种灵长类动物和一种scandentian动物的VII神经元数量进行了立体分析。采用系统发育比较统计学方法,发现灵长类动物的类群大小与VII神经元数量(按髓质体积调整)之间没有相关性。然而,类人猿和人类显示出与他们的髓质大小相符的更多的VII神经元。
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引用次数: 80
Developmentally regulated expression of Shh and Ihh in the developing mouse cranial base: comparison with Sox9 expression. 发育中的小鼠颅底Shh和Ihh的发育调控表达:与Sox9表达的比较
Xuguang Nie, Keijo Luukko, Inger Hals Kvinnsland, Päivi Kettunen

The cranial base, located between the cranial vault and the facial bones, plays an important role in integrated craniofacial development and growth. Transgenic Shh and Sox9-deficient mice show similar defects in cranial base patterning. Therefore, in order to examine potential interactions of Shh, Ihh, another member of the Hh family, and Sox9 during cranial base development and growth, we investigated their cellular mRNA expression domains in the embryonic (E) and early postnatal (PN) cranial base from E10 to PN5 using sectional radioactive 35-S in situ hybridization. Of the Hhs, Shh was observed in the foregut epithelium and the notochord, while Sox9 showed broad expression in the loose mesenchyme of the cranial base area during E10-E11. Subsequently, from E12 onward, all genes were observed in the developing cranial base, and after birth the genes were prominently colocalized in the prehypertrophic chondrocytes of the synchondroses. Collectively, these data suggest that Hh-Sox9 auto- and paracrine signaling interactions may provide a critical mechanism for regulating the patterning of the cranial base as well as for its development and growth.

颅底位于颅穹窿和面骨之间,在颅面发育和生长中起着重要作用。转基因Shh和sox9缺陷小鼠在颅底模式上表现出相似的缺陷。因此,为了研究Shh、Ihh (Hh家族的另一个成员)和Sox9在颅底发育和生长过程中的潜在相互作用,我们使用断层放射性35-S原位杂交技术研究了它们在胚胎(E)和出生后早期(PN)从E10到PN5颅底的细胞mRNA表达域。在Hhs中,Shh在前肠上皮和脊索中观察到,而Sox9在E10-E11期间在颅底区松散间质中广泛表达。随后,从E12开始,所有基因都在发育中的颅底被观察到,出生后,这些基因显著地共定位在软骨软骨的前肥大软骨细胞中。总的来说,这些数据表明Hh-Sox9自动和旁分泌信号相互作用可能为调节颅底模式及其发育和生长提供了关键机制。
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引用次数: 25
Vitamin A storage in hepatic stellate cells in the regenerating rat liver: with special reference to zonal heterogeneity. 再生大鼠肝星状细胞中维生素A的储存:特别参考地带性异质性。
Nobuyo Higashi, Mitsuru Sato, Naosuke Kojima, Toshiaki Irie, Koichi Kawamura, Ayako Mabuchi, Haruki Senoo
Under physiological conditions, hepatic stellate cells (HSCs) within liver lobules store about 80% of the total body vitamin A in lipid droplets in their cytoplasm, and these cells show zonal heterogeneity in terms of vitamin A-storing capacity. Vitamin A is essential for the growth and differentiation of cells, and it is well known that liver cells including HSCs show a remarkable growth capacity after partial hepatectomy (PHx). However, the status of vitamin A storage in HSCs in the liver regeneration is not yet known. Therefore, we conducted the present study to examine vitamin A storage in these cells during liver regeneration. Morphometry at the electron microscopic level, fluorescence microscopy for vitamin A autofluorescence, and immunofluorescence microscopy for desmin and alpha-smooth muscle actin (alpha-SMA) were performed on sections of liver from male Wistar strain rats at various times after the animal had been subjected to 70% PHx. The mean area of vitamin A-storing lipid droplets per HSC gradually decreased toward 3 days after PHx, and then returned to normal within 14 days after it. However, the heterogeneity of vitamin A-storing lipid droplet area per HSC within the hepatic lobule disappeared after PHx and did not return to normal by 14 days thereafter, even though the liver volume had returned to normal. These results suggest that HSCs alter their vitamin A-storing capacity during liver regeneration and that the recovery of vitamin A homeostasis requires a much longer time than that for liver volume.
生理条件下,肝小叶内的肝星状细胞(HSCs)在其细胞质脂滴中储存约80%的体内维生素A,这些细胞在维生素A储存能力方面具有地带性异质性。维生素A对细胞的生长和分化至关重要,众所周知,肝细胞包括造血干细胞在部分肝切除术(PHx)后表现出显著的生长能力。然而,维生素A储存在造血干细胞在肝脏再生中的地位尚不清楚。因此,我们进行了本研究,以检查肝脏再生过程中这些细胞中的维生素A储存。用荧光显微镜观察维生素A自身荧光,免疫荧光显微镜观察聚乳酸蛋白和α -平滑肌肌动蛋白(α - sma)。每个HSC储存维生素a的脂滴的平均面积在服药后3天逐渐减小,在服药后14天恢复正常。然而,在PHx后,肝小叶内每个HSC储存维生素a脂滴面积的异质性消失,并且在此后的14天内没有恢复正常,尽管肝脏体积已经恢复正常。这些结果表明,造血干细胞在肝脏再生过程中改变了其维生素A储存能力,并且维生素A稳态的恢复需要比肝脏容量恢复更长的时间。
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引用次数: 28
Software system for three-dimensional volumetric reconstruction of histological sections: a case study for the snake chondrocranium. 组织切片三维体积重建的软件系统:蛇软骨头盖骨的案例研究。
Clarice Hofstadler-Deiques, Marcelo Walter, Fábio Mierlo, Rodrigo Ruduit

Volumetric digital computer-assisted reconstruction of histological sections is an attractive possibility for developmental studies. Commercial solutions are very expensive for many educational institutions. Therefore, we developed a software system for three-dimensional reconstruction of anatomical virtual models. The input data for the system are the digitized images from the histological samples of the chondrocranium of two crotalines, Bothrops jararaca and Crotalus durissus terrificus, and one colubrid, Philodryas olfersii, using a stereomicroscope connected to a digital camera. These images are then manually registered and segmented. We use computer graphics visualization algorithms such as marching cubes and ray casting to generate three-dimensional visualizations of the volumes. The results show that the digital reconstruction is as good as the manual reconstruction with the advantages of speed of reconstruction, accuracy, and flexibility to handle and study the volume. Compared with commercial options, our system has approximately the same features, and it is available free for the scientific community.

组织切片的体积数字计算机辅助重建是一种有吸引力的发展研究的可能性。对于许多教育机构来说,商业解决方案非常昂贵。因此,我们开发了一个用于解剖虚拟模型三维重建的软件系统。该系统的输入数据是两种Crotalus (Bothrops jararaca和Crotalus durissus terrificus)和一种Crotalus (Philodryas olfersii)的软骨颅骨组织学样本的数字化图像,这些样本使用连接到数码相机的立体显微镜。然后手动对这些图像进行配准和分割。我们使用计算机图形可视化算法,如行进立方体和光线投射来生成三维可视化的体积。结果表明,数字重建与人工重建一样,具有重建速度快、精度高、处理和研究体积灵活等优点。与商业选择相比,我们的系统具有大致相同的功能,并且可以免费提供给科学界。
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引用次数: 8
Different levels of the neuronal nitric oxide synthase isoform modulate the rate of osteoclastic differentiation of TIB-71 and CRL-2278 RAW 264.7 murine cell clones. 不同水平的神经元一氧化氮合酶异构体调节TIB-71和CRL-2278 RAW 264.7小鼠细胞克隆的破骨分化率。
Vanessa Nicolin, Cristina Ponti, Paola Narducci, Vittorio Grill, Roberta Bortul, Marina Zweyer, Mauro Vaccarezza, Giorgio Zauli

It has been clearly established that osteoclasts, which play a crucial role in bone resorption, differentiate from hematopoietic cells belonging to the monocyte/macrophage lineage in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). We have here investigated the M-CSF- and RANKL-induced osteoclastic differentiation of two distinct clones of the murine monocytic/macrophagic RAW 264.7 cell line, known as TIB-71 and CRL-2278, the latter cell clone being defective for the expression of the inducible nitric oxide synthase isoform in response to interferon-gamma or lipopolysaccharide. CRL-2278 cells demonstrated a more rapid osteoclastic differentiation than TIB-71 cells, as documented by morphology, tartrate-resistant acid phosphatase positivity, and bone resorption activity. The enhanced osteoclastic differentiation of CRL-2278 was accompanied by a higher rate of cells in the S/G2-M phases of cell cycle as compared to TIB-71. The analysis of nitric oxide synthase (NOS) isoforms clearly demonstrated that only neuronal NOS was detectable at high levels in CRL-2278 but not in TIB cells under all tested conditions. Moreover, the broad inhibitor of NOS activity L-NAME significantly inhibited osteoclastic differentiation of CRL-2278 cells. Altogether, these results demonstrate that a basal constitutive neuronal NOS activity positively affects the RANKL/M-CSF-related osteoclastic differentiation.

破骨细胞在骨吸收中起着至关重要的作用,在巨噬细胞集落刺激因子(M-CSF)和nf - κ b配体受体激活剂(RANKL)的存在下,破骨细胞从单核/巨噬细胞谱系的造血细胞分化而来。我们在这里研究了M-CSF和rankl诱导的小鼠单核/巨噬细胞RAW 264.7细胞系两个不同克隆的破骨细胞分化,称为TIB-71和CRL-2278,后者的细胞克隆对干扰素或脂多糖的诱导型一氧化氮合酶异构体的表达有缺陷。CRL-2278细胞表现出比TIB-71细胞更快的破骨细胞分化,这是由形态学、抗酒石酸酸性磷酸酶阳性和骨吸收活性证明的。与TIB-71相比,CRL-2278增强的破骨细胞分化伴随着更高的细胞周期S/G2-M期的细胞率。一氧化氮合酶(NOS)异构体分析清楚地表明,在所有测试条件下,只有神经元NOS在CRL-2278中检测到高水平,而在TIB细胞中检测不到。此外,广泛的NOS活性抑制剂L-NAME显著抑制CRL-2278细胞的破骨细胞分化。综上所述,这些结果表明,基础构成神经元NOS活性积极影响RANKL/ m - csf相关的破骨细胞分化。
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引用次数: 12
Development of the articular cavity in the rat temporomandibular joint with special reference to the behavior of endothelial cells and macrophages. 大鼠颞下颌关节腔的发育与内皮细胞和巨噬细胞的行为有关。
Akiko Suzuki, Kayoko Nozawa-Inoue, Nobuyuki Ikeda, Norio Amizuka, Kazuhiro Ono, Ritsuo Takagi, Takeyasu Maeda

Previous developmental studies on the temporomandibular joint (TMJ) have proposed several hypotheses on the formation of its articular cavity. However, detailed information is meager. The present study examined the formation process of the articular cavity in the rat TMJ by immunocytochemistry for CD31, RECA-1, and ED1, which are useful cellular markers for endothelial cells and monocyte/macrophage lineages, respectively. The upper articular cavity formation had begun by embryonic day 21 (E21) and was completed at postnatal day 1 (P1) in advance of the lower cavitation; the latter took place from P1 to P3. The occurrence and distribution pattern of the CD31-, RECA-1-, and ED1-positive cells differed between the upper and lower articular cavity-forming areas: the ED1-positive cells exclusively occurred in the area of the prospective upper articular cavity prior to its formation, while no ED1-positive cell appeared in the lower cavity-forming area. In contrast, the CD31- and RECA-1-positive endothelial cells were restricted to the lower cavity-forming area (never the prospective upper cavity) at E19 and diminished thereafter. Throughout the cavity formation, we failed to find any apoptotic cells in the cavity formation area, indicating no involvement of apoptosis in the cavity formation in TMJ. The present findings on the behaviors of endothelial cells and ED1-positive cells show a possibility of different mechanism in the cavity formation between the upper and lower articular cavities in the rat TMJ. The appearance of ED1-reactive cells and temporal vascularization may play crucial roles in the upper and lower articular cavity formation, respectively.

以往关于颞下颌关节(TMJ)的发育研究对其关节腔的形成提出了几种假说。然而,详细的信息很少。本研究采用免疫细胞化学方法检测了大鼠TMJ关节腔的形成过程,CD31、RECA-1和ED1分别是内皮细胞和单核/巨噬细胞谱系的有用细胞标志物。上关节腔的形成在胚胎第21天(E21)开始,在出生后第1天(P1)完成,下关节腔形成之前;后者发生在P1到P3阶段。CD31-、RECA-1-和ed1阳性细胞在上下关节腔形成区出现和分布模式不同:ed1阳性细胞只出现在预期关节腔形成前的上关节腔区域,而下关节腔形成区未出现ed1阳性细胞。相比之下,CD31-和reca -1阳性内皮细胞在E19时仅限于下腔形成区(而不是预期的上腔),此后逐渐减少。在整个空腔形成过程中,我们在空腔形成区未发现凋亡细胞,说明凋亡未参与TMJ空腔的形成。内皮细胞和ed1阳性细胞的行为表明,大鼠TMJ上下关节腔的形成可能存在不同的机制。ed1反应细胞的出现和颞叶血管化可能分别在上、下关节腔的形成中起关键作用。
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引用次数: 5
Genes critical to vasculogenesis as defined by systematic analysis of vascular defects in knockout mice. 通过对敲除小鼠血管缺陷的系统分析确定的对血管发生至关重要的基因。
W Scott Argraves, Christopher J Drake

To identify genes important to the process of vasculogenesis, we evaluated embryonic vascular anomalies from 100 mouse knockout studies using a novel meta-analysis approach. By applying this method, termed approach for ranking of embryonic vascular anomalies (AREVA), rank scores were calculated for each knockout based on the occurrence of vascular defects during periods of vasculogenesis in specific embryonic regions. As a result, 12 genes (fibronectin, VEGFR-1/Flt-1, VEGFR-2/Flk-1, alpha 5 integrin, Tek/Tie2, VE-cadherin, VEGFA, connexin 45, ShcA, cytochrome P450 reductase, CD148/DEP-1, and EphrinB2) were determined to play critical roles in vasculogenesis. Functional categorization of these genes revealed the fundamental importance of VEGF signaling since 10 of the 12 genes (fibronectin, VEGFR-1/Flt-1, VEGFR-2/Flk-1, alpha 5 integrin, VE-cadherin, VEGFA, ShcA, cytochrome P450 reductase, CD148/DEP-1, and EphrinB2) relate to this pathway. Furthermore, the findings highlight a potential network for regulating VEGF signaling involving integration of fibronectin, EphrinB2, Tie2, and connexin 45 signaling pathways via the ShcA/Ras/Raf/Mek/Erk cascade. In addition to retrospective application of AREVA as done herein, AREVA can be used prospectively to determine the relevancy to vasculogenesis of newly inactivated genes.

为了确定对血管发生过程重要的基因,我们使用一种新的荟萃分析方法评估了100只小鼠基因敲除研究中的胚胎血管异常。通过应用这种称为胚胎血管异常排序法(AREVA)的方法,根据特定胚胎区域血管形成期间血管缺陷的发生情况,计算每个基因敲除的等级分数。结果,12个基因(纤维连接蛋白、VEGFR-1/Flt-1、VEGFR-2/Flk-1、α 5整合素、Tek/Tie2、VE-cadherin、VEGFA、连接蛋白45、ShcA、细胞色素P450还原酶、CD148/DEP-1和EphrinB2)被确定在血管发生中发挥关键作用。这些基因的功能分类揭示了VEGF信号传导的基本重要性,因为12个基因中有10个(纤维连接蛋白、VEGFR-1/Flt-1、VEGFR-2/Flk-1、α 5整合素、VE-cadherin、VEGFA、ShcA、细胞色素P450还原酶、CD148/DEP-1和EphrinB2)与这一途径有关。此外,研究结果强调了通过ShcA/Ras/Raf/Mek/Erk级联调节VEGF信号通路的潜在网络,涉及纤维连接蛋白、EphrinB2、Tie2和connexin 45信号通路的整合。除了本文所述的回顾性应用AREVA外,AREVA还可用于前瞻性地确定新失活基因与血管发生的相关性。
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引用次数: 57
期刊
The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology
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