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.     

An autopodial-like pattern of Hox expression in the fins of a basal actinopterygian fish

Comparative analyses of Hox gene expression and regulation in teleost fish and tetrapods support the long-entrenched notion that the distal region of tetrapod limbs, containing the wrist, ankle and digits, is an evolutionary novelty. Data from fossils support the notion that the unique features of tetrapod limbs were assembled over evolutionary time in the paired fins of fish. The challenge in linking developmental and palaeontological approaches has been that developmental data for fins and limbs compare only highly derived teleosts and tetrapods; what is lacking are data from extant taxa that retain greater portions of the fin skeletal morphology considered primitive to all bony fish. Here, we report on the expression and function of genes implicated in the origin of the autopod in a basal actinopterygian, Polyodon spathula. Polyodon exhibits a late-phase, inverted collinear expression of 5' HoxD genes, a pattern of expression long considered a developmental hallmark of the autopod and shown in tetrapods to be controlled by a 'digit enhancer' region. These data show that aspects of the development of the autopod are primitive to tetrapods and that the origin of digits entailed the redeployment of ancient patterns of gene activity.     

T-box gene tbx5 is essential for formation of the pectoral limb bud

The T-box genes Tbx4 and Tbx5 have been shown to have key functions in the specification of the identity of the vertebrate forelimb (Tbx5) and hindlimb (Tbx4). Here we show that in zebrafish, Tbx5 has an additional early function that precedes the formation of the limb bud itself. Functional knockdown of zebrafish tbx5 through the use of an antisense oligonucleotide resulted in a failure to initiate fin bud formation, leading to the complete loss of pectoral fins. The function of the tbx5 gene in the development of zebrafish forelimbs seems to involve the directed migration of individual lateral-plate mesodermal cells into the future limb-bud-producing region. The primary defect seen in the tbx5-knockdown phenotype is similar to the primary defects described in known T-box-gene mutants such as the spadetail mutant of zebrafish and the Brachyury mutant of the mouse, which both similarly exhibit an altered migration of mesodermal cells. A common function for many of the T-box genes might therefore be in mediating the proper migration and/or changes in adhesive properties of early embryonic cells.     

Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function

Vertebrate HoxA and HoxD cluster genes are required for proper limb development. However, early lethality, compensation and redundancy have made a full assessment of their function difficult. Here we describe mice that are lacking all Hoxa and Hoxd functions in their forelimbs. We show that such limbs are arrested early in their developmental patterning and display severe truncations of distal elements, partly owing to the absence of Sonic hedgehog expression. These results indicate that the evolutionary recruitment of Hox gene function into growing appendages might have been crucial in implementing hedgehog signalling, subsequently leading to the distal extension of tetrapod appendages. Accordingly, these mutant limbs may be reminiscent of an ancestral trunk extension, related to that proposed for arthropods.     

大鳍鳠臀鳍和脂鳍的比较组织学研究

大鳍鳠臀鳍和脂鳍均是皮肤特化的产物．臀鳍的组织结构可分为表皮层、胶原纤维层、胶原下层和鳍条４部分；脂鳍可分为表皮层、胶原纤维层和脂肪层．臀鳍和脂鳍的表层均与皮肤的表皮相似，而发达的胶原纤维层与皮肤真皮的致密层相当．臀鳍的胶原下层、脂鳍的脂肪层与皮下层相当，而鳍条则是矿化的结缔组织．从特化程度来看，脂鳍的特化程度不如臀鳍高，表明脂鳍应是奇鳍褶的痕迹器官．     

The novel Cer-like protein Caronte mediates the establishment of embryonic left-right asymmetry.

In the chick embryo, left-right asymmetric patterns of gene expression in the lateral plate mesoderm are initiated by signals located in and around Hensen's node. Here we show that Caronte (Car), a secreted protein encoded by a member of the Cerberus/Dan gene family, mediates the Sonic hedgehog (Shh)-dependent induction of left-specific genes in the lateral plate mesoderm. Car is induced by Shh and repressed by fibroblast growth factor-8 (FGF-8). Car activates the expression of Nodal by antagonizing a repressive activity of bone morphogenic proteins (BMPs). Our results define a complex network of antagonistic molecular interactions between Activin, FGF-8, Lefty-1, Nodal, BMPs and Car that cooperate to control left-right asymmetry in the chick embryo.     

The pectoral fin of Tiktaalik roseae and the origin of the tetrapod limb

Wrists, ankles and digits distinguish tetrapod limbs from fins, but direct evidence on the origin of these features has been unavailable. Here we describe the pectoral appendage of a member of the sister group of tetrapods, Tiktaalik roseae, which is morphologically and functionally transitional between a fin and a limb. The expanded array of distal endochondral bones and synovial joints in the fin of Tiktaalik is similar to the distal limb pattern of basal tetrapods. The fin of Tiktaalik was capable of a range of postures, including a limb-like substrate-supported stance in which the shoulder and elbow were flexed and the distal skeleton extended. The origin of limbs probably involved the elaboration and proliferation of features already present in the fins of fish such as Tiktaalik.     

开缝翅片流动和传热性能的实验研究及数值模拟

对2排X型双向开缝翅片管换热器空气侧的传热及阻力性能进行了实验研究, 在实验的 Re范围内得出了传热和阻力的性能关联式及特性曲线.比较得出,开缝翅片的传热性能远高于平直翅片,与单向开缝翅片相比,X型双向开缝翅片的性能更好.通过数值模拟得出了 X型双向开缝翅片的效率计算曲线.应用场协同原理,对数值模拟得到的气流在2片翅片之间的温度场、速度场、对流换热系数及压降在流动方向上的沿程变化进行了分析.结果表明,开缝翅片有效强化传热的根本原因是翅片开缝后改善了速度和温度梯度的协同性.     

高效翅柱复合型散热器的流动与散热性能研究

针对平板翅片式散热器存在的不足,提出了一种翅片间设有钉柱的翅柱复合型散热器.钉柱能够使通过该散热器的气流受到扰动,从而提高其散热性能.通过对2种散热器通道内的流动换热进行数值计算和实验验证,结果表明:在相同的风速下,翅柱式散热器表面的Nusselt数比板翅式散热器高30%～50%;在相同的泵送功率下,翅柱式散热器的收益因子比板翅式散热器约高20%.因此,在相同的工况下,翅柱式散热器具有更好的散热性能,并具有可靠性高、使用成本低的优点,在电力电子设备的冷却中具有较高的使用价值.     

Cell-autonomous action of zebrafish spt-1 mutation in specific mesodermal precursors

In zebrafish, as in Xenopus, the well-orchestrated cell movements of gastrulation can be dissected into several components, including epiboly, involution, convergence and extension. Embryos homozygous for the recessive lethal mutation spt-1(b104) or 'spadetail' have a complex set of defects in the trunk of the embryo that may arise secondarily after loss of one of these movements, convergence, from those precursors that would normally have given rise to trunk somitic mesoderm. We have now tested this hypothesis by transplanting cells between wild-type and mutant embryos, to identify the cells that spt-1 affects directly. Our results show that the mutation autonomously affects only those mesodermal precursors located along the lateral margin of the early gastrula blastoderm. Other mesodermal cells and all ectodermal precursors seem not to require function of the wild-type gene. Our findings reveal an unexpectedly delicate genetic control of vertebrate gastrulation.     

Retinoic acid signalling links left-right asymmetric patterning and bilaterally symmetric somitogenesis in the zebrafish embryo

During embryogenesis, cells are spatially patterned as a result of highly coordinated and stereotyped morphogenetic events. In the vertebrate embryo, information on laterality is conveyed to the node, and subsequently to the lateral plate mesoderm, by a complex cascade of epigenetic and genetic events, eventually leading to a left-right asymmetric body plan. At the same time, the paraxial mesoderm is patterned along the anterior-posterior axis in metameric units, or somites, in a bilaterally symmetric fashion. Here we characterize a cascade of laterality information in the zebrafish embryo and show that blocking the early steps of this cascade (before it reaches the lateral plate mesoderm) results in random left-right asymmetric somitogenesis. We also uncover a mechanism mediated by retinoic acid signalling that is crucial in buffering the influence of the flow of laterality information on the left-right progression of somite formation, and thus in ensuring bilaterally symmetric somitogenesis.     

计算肋片散热的一种改进方法

通过对二维肋片导热机理的分析，提出了一种改进的计算二维肋片散热和温度分布的一维近似方法。这一方法与经典的一维近似方法一样简单实用，并可套用经典方法的所有公式和图表，分别用改进的一维近似方法、经典一维方法和二维方法对工程中几种常见肋片进行了计算并加以比较。结果表明，一维近似方法较经典一维方法的精度有明显提高。     

错齿翅片的传热与阻力性能试验

对9种不同结构参数的错齿翅片进行传热和流动阻力性能试验,分析比较翅片的间距、高度和节距等结构参数对其传热因子和阻力性能的影响.同时,利用场协同原理揭示错齿翅片强化传热的机理,并采用单位面积泵功率的评价方法,比较9种翅片的强化传热效果.结果表明,错齿翅片的节距和长度对其热工性能影响最为显著.     

基于单刃-圆锥面刀具的三维整体外翅片成形机理

采用单刃-圆锥面刀具加工三维整体外翅片管,研究了翅片成形过程及圆锥面半径对翅片成形的影响,分析了翅片微观形貌的形成机理及加工参数对翅片形貌的影响.翅片成形机理在于单刃-圆锥面刀具切削时能将工件表层金属与基体分离但并不去除,被分离的金属在圆锥面的挤压下形成翅片.翅片成形过程可分为犁切分离、滑动挤压和成翅3个阶段,较大的圆弧半径有利于翅片的成形.翅片顶部有一条贯穿整个翅片的微裂缝,使翅片在微观上成为双翅片;随着犁切深度的增加,翅片厚度增加;随着进给量的增大,翅片间距增加.     

Mox2 is a component of the genetic hierarchy controlling limb muscle development.

The skeletal muscles of the limbs develop from myogenic progenitors that originate in the paraxial mesoderm and migrate into the limb-bud mesenchyme. Among the genes known to be important for muscle development in mammalian embryos are those encoding the basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs; MyoD, Myf5, myogenin and MRF4) and Pax3, a paired-type homeobox gene that is critical for the development of limb musculature. Mox1 and Mox2 are closely related homeobox genes that are expressed in overlapping patterns in the paraxial mesoderm and its derivatives. Here we show that mice homozygous for a null mutation of Mox2 have a developmental defect of the limb musculature, characterized by an overall reduction in muscle mass and elimination of specific muscles. Mox2 is not needed for the migration of myogenic precursors into the limb bud, but it is essential for normal appendicular muscle formation and for the normal regulation of myogenic genes, as demonstrated by the downregulation of Pax3 and Myf5 but not MyoD in Mox2-deficient limb buds. Our findings show that the MOX2 homeoprotein is an important regulator of vertebrate limb myogenesis.     

新型开窗翅片板翅换热器热工性能试验

对9种不同结构参数的新型开窗翅片进行传热和流动阻力性能试验.在此基础上,给出传热因子和摩擦因子随雷诺数的变化曲线,并比较翅片间距和翅片长度等结构参数对其表面换热和阻力性能的影响.同时,利用单位传热面积泵功率和面积优化因子分析比较各翅片的综合强化传热效果.试验结果表明,新型开窗翅片的翅片间距对表面传热因子和阻力性能影响较为显著.