Genetic ablation reveals that the roof plate is essential for dorsal interneuron specification

During neural development in vertebrates, a spatially ordered array of neurons is generated in response to inductive signals derived from localized organizing centres. One organizing centre that has been proposed to have a role in the control of neural patterning is the roof plate. To define the contribution of signals derived from the roof plate to the specification of neuronal cell types in the dorsal neural tube, we devised a genetic strategy to ablate the roof plate selectively in mouse embryos. Embryos without a roof plate lack all the interneuron subtypes that are normally generated in the dorsal third of the neural tube. Using a genetically based lineage analysis and in vitro assays, we show that the loss of these neurons results from the elimination of non-autonomous signals provided by the roof plate. These results reveal that the roof plate is essential for specifying multiple classes of neurons in the mammalian central nervous system.     

The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system

The floor plate is a set of epithelial cells present in the ventral midline of the neural tube in vertebrates that seems to have an important role in the developmental patterning of central nervous system fibre pathways, and arrangements of specific neurons. The floor plate arises from dorsal ectodermal cells closely associated with the mesoderm that forms notochord, and it may depend on interactions from the notochord for its specification. To learn the nature of these interactions we have analysed mutations in zebrafish (Brachydanio rerio). We report here that in wild-type embryos the floor plate develops as a simply organized single cell row, but that its development fails in embryos bearing the newly discovered zygotic lethal 'cyclops' mutation, cyc-1(b16). Mosaic analysis establishes that cyc-1 blocks floor plate development autonomously and reveals the presence of homeogenetic induction between floor plate cells.     

Tbx6-dependent Sox2 regulation determines neural or mesodermal fate in axial stem cells

The classical view of neural plate development held that it arises from the ectoderm, after its separation from the mesodermal and endodermal lineages. However, recent cell-lineage-tracing experiments indicate that the caudal neural plate and paraxial mesoderm are generated from common bipotential axial stem cells originating from the caudal lateral epiblast. Tbx6 null mutant mouse embryos which produce ectopic neural tubes at the expense of paraxial mesoderm must provide a clue to the regulatory mechanism underlying this neural versus mesodermal fate choice. Here we demonstrate that Tbx6-dependent regulation of Sox2 determines the fate of axial stem cells. In wild-type embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the caudal lateral epiblast, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expression in the neural plate. In contrast, the cells destined to become mesoderm activate Tbx6 and turn off enhancer N1 before migrating into the paraxial mesoderm compartment. In Tbx6 mutant embryos, however, enhancer N1 activity persists in the paraxial mesoderm compartment, eliciting ectopic Sox2 activation and transforming the paraxial mesoderm into neural tubes. An enhancer-N1-specific deletion mutation introduced into Tbx6 mutant embryos prevented this Sox2 activation in the mesodermal compartment and subsequent development of ectopic neural tubes, indicating that Tbx6 regulates Sox2 via enhancer N1. Tbx6-dependent repression of Wnt3a in the paraxial mesodermal compartment is implicated in this regulatory process. Paraxial mesoderm-specific misexpression of a Sox2 transgene in wild-type embryos resulted in ectopic neural tube development. Thus, Tbx6 represses Sox2 by inactivating enhancer N1 to inhibit neural development, and this is an essential step for the specification of paraxial mesoderm from the axial stem cells.     

轨道交通混凝土箱梁低频噪声贡献源及空间分布

以轨道交通双线混凝土简支箱梁为研究对象,建立车辆-轨道-箱梁有限元模型和箱梁振动-辐射噪声有限元-无限元模型。结合现场试验,计算了箱梁整体和各板件的声场分布及各板件的声压贡献。结果表明,有限元-无限元模型能够准确预测箱梁的结构噪声;腹板对梁侧声压贡献较小;近场声压主要受底板的影响,其次是翼板;远场声压主要受底板和顶板的影响;在底板以下空间,底板对声场起控制作用;箱梁同一高度,顶板声压贡献略大于翼板,两者起主要作用;顶板以上区域,顶板声压贡献远大于其他板件。     

Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain

The Drosophila fruitless (fru) gene product Fru has been postulated to be a neural sex determination factor that directs development of the central nervous system (CNS), thereby producing male-typical courtship behaviour and inducing male-specific muscle. Male-specific Fru protein is expressed in small groups of neurons scattered throughout the CNS of male, but not female, Drosophila. Collectively, these observations suggest that Fru 'masculinizes' certain neurons, thereby establishing neural substrates for male-typical behaviour. However, specific differences between neurons resulting from the presence or absence of Fru are unknown. Previous studies have suggested that Fru might result in sexual differences in the CNS at the functional level, as no overt sexual dimorphism in CNS structure was discernible. Here we identify a subset of fru-expressing interneurons in the brain that show marked sexual dimorphism in their number and projection pattern. We also demonstrate that Fru supports the development of neurons with male-specific dendritic fields, which are programmed to die during female development as a result of the absence of Fru. Thus, Fru expression can produce a male-specific neural circuit, probably used during heterosexual courtship, by preventing cell death in identifiable neurons.     

青岛文昌鱼hedgehog基因表达图式的研究

Ｈｅｄｇｅｈｏｇ（ｈｈ）家族基因编码一类分泌性信号分子,在果蝇的体节和成虫盘等的图式形成和脊椎动物脊索、神经管、体节和肢等的发育中起着关键作用．探讨原索动物文昌鱼ｈｈ基因的功能,对于研究脊椎动物发育机制的进化具有重要意义．本文报道了用整体原位杂交方法,研究不同发育时期文昌鱼胚胎和幼体ｈｈ基因表达图式的结果,并对文昌鱼ｈｈ基因的功能和ｈｈ家族同源基因功能的演化进行了讨论．文昌鱼ｈｈ基因在脊索和神经管中的表达图式与脊椎动物Ｓｈｈ基因相似,其功能可能是介导脊索的诱导．     

Retinoic acid causes an anteroposterior transformation in the developing central nervous system

All-trans retinoic acid (RA) is well known as a biologically active form of vitamin A and a teratogen. The identification of nuclear receptors for this ligand suggests strongly that it is an endogenous signal molecule, and measurements of RA and teratogenic manipulations suggest further that RA is a morphogen specifying the anteroposterior axis during limb development. Besides the limb, RA and other retinoids affect development of other organs, including the central nervous system (CNS). None of these other effects has been investigated in detail. Our purpose here was to begin analysing the effects of RA on CNS development in Xenopus laevis. We find that RA acts on the developing CNS, transforming anterior neural tissue to a posterior neural specification. These and other findings raise the possibility that RA mediates an inductive interaction regulating anteroposterior differentiation within the CNS. Following recent reports implicating transforming growth factor-beta 2-like and fibroblast growth factor-like factors in mesoderm induction, this indicates that a different type of signal molecule (working through a nuclear receptor, not a plasma membrane receptor) might mediate inductive cell interactions during early embryonic development.     

Polarizing activity and retinoid synthesis in the floor plate of the neural tube

In many developing organisms the establishment of axial polarity and the patterning of cells depend on local signals that derive from restricted regions of the embryo. In vertebrate embryos, the origins of tissue polarity have been examined extensively in the developing limb. The anteroposterior pattern of the chick limb seems to be controlled by a morphogen, possibly retinoic acid, that is enriched in a region of the limb known as the zone of polarizing activity (ZPA). Certain tissues other than the ZPA have also shown polarizing activity experimentally in the chick limb, raising the possibility that signalling molecules involved in pattern formation in different embryonic tissues are conserved. Here we provide evidence that a similar polarizing activity is also present in a restricted region of the developing central nervous system (CNS). We show that a specialized group of neural cells termed the floor plate, but not other regions of the CNS, mimics the ZPA in respecifying the digit pattern in the developing chick limb. In addition, using an in vitro biochemical assay, we show that the floor plate can synthesize retinoic acid and 3,4-didehydroretinol, the precursor of a second morphogenetically active retinoid, 3,4-didehydroretinoic acid. These results show that the floor plate is a local source of a ZPA-like polarizing signal, possibly a retinoid, which may regulate the pattern of cell differentiation in the developing CNS.     

Regulation of repulsion versus adhesion by different splice forms of an Eph receptor

Eph tyrosine kinase receptors and their membrane-bound ephrin ligands mediate cell interactions and participate in several developmental processes. Ligand binding to an Eph receptor results in tyrosine phosphorylation of the kinase domain, and repulsion of axonal growth cones and migrating cells. Here we report that a subpopulation of ephrin-A5 null mice display neural tube defects resembling anencephaly in man. This is caused by the failure of the neural folds to fuse in the dorsal midline, suggesting that ephrin-A5, in addition to its involvement in cell repulsion, can participate in cell adhesion. During neurulation, ephrin-A5 is co-expressed with its cognate receptor EphA7 in cells at the edges of the dorsal neural folds. Three different EphA7 splice variants, a full-length form and two truncated versions lacking kinase domains, are expressed in the neural folds. Co-expression of an endogenously expressed truncated form of EphA7 suppresses tyrosine phosphorylation of the full-length EphA7 receptor and shifts the cellular response from repulsion to adhesion in vitro. We conclude that alternative usage of different splice forms of a tyrosine kinase receptor can mediate cellular adhesion or repulsion during embryonic development.     

黑瓷复合陶瓷太阳板集热系统的应用研究

研发了一种与建筑一体化的新型高效平板太阳能集热体黑瓷复合陶瓷太阳板。该集热体以普通瓷土为原料配制泥浆注浆成型,表面喷涂以工业废弃物提钒尾渣为原料调配的钒钛黑瓷泥浆层,干燥后经连续辊道窑1 200 ℃烧制而成,阳光吸收比为0.95。介绍了陶瓷太阳板房顶集热系统的构建方法,该系统与建筑共用结构层、保温层、防水层,与建筑一体化、同寿命,隔热、保温效果优于普通房顶。通过建筑实例对该集热系统的集热效率与真空玻璃管热水器进行测试对比,得出集热系统日得热量为8.6 MJ/m²,远高于真空玻璃管热水器和国家标准的7.0 MJ/m² ,可实现太阳能使用成本低于常规能源。     

Cell lineage analysis reveals multipotency of some avian neural crest cells

A major question in developmental biology is how precursor cells give rise to diverse sets of differentiated cell types. In most systems, it remains unclear whether the precursors can form many or all cell types (multipotent or totipotent), or only a single cell type (predetermined). The question of cell lineage is central to the neural crest because it gives rise to numerous and diverse derivatives including peripheral neurons, glial and Schwann cells, pigment cells, and cartilage. Although the sets of derivatives arising from different populations of neural crest cells have been well-documented, relatively little is known about the developmental potentials of individual neural crest cells. We have iontophoretically microinjected the vital dye, lysinated rhodamine dextran (LRD) into individual dorsal neural tube cells to mark unambiguously their descendants. Many of the resulting labelled clones consisted of multiple cell types, as judged by both their location and morphology. Cells as diverse as sensory neurons, presumptive pigment cells, ganglionic supportive cells, adrenomedullary cells and neural tube cells were found within individual clones. Our results indicate that at least some neural crest cells are multipotent before their departure from the neural tube.     

Division and differentiation of isolated CNS blast cells in microculture

The mechanism of transformation of the overtly similar cells of the neural plate into the numerous and diverse cell types of the mature vertebrate central nervous system (CNS) can better be understood by studying the clonal development of isolated CNS precursor cells. Here I describe a culture system in which blast cells (cells capable of division) isolated from embryonic day 13.5-14.5 rat forebrain can divide and differentiate into a variety of clonal types. Most clones contain only neurons or glia; 22% contain both neurons and non-neuronal cells. For the division of blast cells, live conditioning cells need to be present indicating that environmental signals influence proliferation. Heterogeneous clones develop in homogeneous culture conditions, so factors intrinsic to the blast cells are probably important in determining the number and type of clonal progeny.     

A gene expression atlas of the central nervous system based on bacterial artificial chromosomes

The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.     

顶板来压后工作面端头顶板的结构形式、稳定性及支护措施

本文在相似材料模拟实验及现场观察的基础上,就客观上存在的端头顶板结构——弧三角形悬板,运用板的极限分析方法,分析了它的稳定性,明确指出:在能够形成这一端头结构的采场条件下,端头顶板的稳定性好于工作面内的顶板,对于合理地进行顶板支护具有指导意义。     

老顶的初次断裂步距和周期断裂步距

本文应用板的极限分析法求老顶的断裂步距,从而解决了按板模型周现有的方法不能计算老顶周期断裂步距的问题这种方法的另一个显著的优点是它不但适用于矩形采空区而且也适用于非矩形采空区。作者导出了几种常见开采边界老顶的初次、周期断裂步距的表达式,并通过算例说明了公式的用法。本文最后讨论了工作面长度和开采边界对老顶断裂步距的影响,提出了对坚硬顶板控制有实际意义的工作面临界长度的概念。图5,表1,参6.     

Migratory neural crest-like cells form body pigmentation in a urochordate embryo

The neural crest, a source of many different cell types in vertebrate embryos, has not been identified in other chordates. Current opinion therefore holds that neural crest cells were a vertebrate innovation. Here we describe a migratory cell population resembling neural crest cells in the ascidian urochordate Ecteinascidia turbinata. Labelling of embryos and larvae with the vital lipophilic dye DiI enabled us to detect cells that emerge from the neural tube, migrate into the body wall and siphon primordia, and subsequently differentiate as pigment cells. These cells express HNK-1 antigen and Zic gene markers of vertebrate neural crest cells. The results suggest that migratory cells with some of the features of neural crest cells are present in the urochordates. Thus, we propose a hypothesis for neural crest evolution beginning with the release of migratory cells from the CNS to produce body pigmentation in the common ancestor of the urochordates and vertebrates. These cells may have gained additional functions or were joined by other cell types to generate the variety of derivatives typical of the vertebrate neural crest.