Somitogenesis in the mouse embryo

This report describes the initiation of somitogenesis in the mouse embryo. Correlations are made with fibronectin distribution around the unsegmented mesoderm and the distribution of cytoskeletal elements within the cells as they undergo morphogenetic movements. The same temporal and topological changes in fibronectin, laminin, and cytoskeletal elements are seen in mouse somitogenesis as in the chick embryo. A notable exception is that the epithelial stage of somitogenesis in the mouse does not form a closed vesicle as it does in the chick. In the mouse the mesial portion of the forming somite does not become epithelial before the migration of sclerotomal cells.     

The Origin of the Chordates

The study of development and comparisons of the adult structures of the several groups of protochordate animals reveals something of their interrelationships and origin. The hemichordates are perhaps closer to the echinoderms than to the chordates, but these groups appear to have been derived from a bilaterally symmetrical dipleurula ancestor, not from a sessile pterobranch-like form. The origin of the chordates is speculative but the idea of a prototunicate stage is rejected. The tunicate is viewed as a highly modified end product, with fewer similarities to the ancestral form than amphioxus. Amphioxus is quite suggestive of the vertebrate, yet it is more like the tunicate in the details of its embryology and along with that rather extreme peripheral group is best thought of as constituting a subphylum, the Acraniata. The idea of the early vertebrate as a filter feeder must be rejected since it is assumed here that perfection of that function led to a sessile or inactive way of life (as in the acraniates or lamprey larva) and failed to lead to the active creature with highly developed sensory, neural, and locomotor systems identified here as the protovertebrate. Further, the muscular plastic pharynx and moveable mouth of the protovertebrate suggest feeding on larger organisms, predation, and the abandonment of ciliary water-current feeding.     

动物体节发生模型及其相关基因研究进展

脊椎动物在胚胎发育的过程中沿身体前后轴形成一定数目的暂时性结构—体节（somite）,随着胚胎的继续发育每个体节分化成为生骨节,生皮节和生肌节,继而生成各种组织。近三十年来,研究者们就体节的发生和发育提出了多种解释模型,这包括时钟波阵面模型,反应扩散模型,时钟诱导模型,时钟痕迹模型等,虽然这些模型能从不同角度不同程度来解释动物体节发生和发育的不同现象, 但无一能够解释体节发生和发育的全部。然而,大多数模型都提出了时钟分割（segmental clock）这一概念。鸡胚中的c-hairy1和c-hairy2,鸡胚、小鼠中的lunatic fringe以及斑马鱼中的her1, Delta C等几种基因的表达图式的研究为模型中分割时钟的存在提供了分子生物学上的有力证据。     

Evidence for the Heparin-Binding Ability of the Ascidian Xlink Domain and Insight into the Evolution of the Xlink Domain in Chordates

The vertebrate Xlink domain is found in two types of genes: lecticans and their associated hyaluronan-and-proteoglycan-binding-link-proteins (HAPLNs), which are components of the extracellular matrix, and those represented by CD44 and stabilins, which are expressed on the surface of lymphocytes. In both types of genes, Xlink functions as a hyaluronan binding domain. We have already reported that protochordate ascidians possess only the latter type of gene. The present analysis of the expression of ascidian Xlink domain genes revealed that these genes function in blood cell migration and apoptosis. While the Xlink domain is found in various metazoans, including ascidians and nematodes, hyaluronan is believed to be specific for vertebrates. In comprehensive genome surveys for hyaluronan synthase (HAS), we found no HAS gene in ascidians. We also established that hyaluronan is absent from the ascidian body biochemically. Therefore, ascidians possess the Xlink domain, but they lack HA. We recovered one ascidian Xlink domain gene that encoded a heparin-binding protein, although it shows no affinity for hyaluronan. Based on these findings, we conclude that in invertebrates, the Xlink domain serves as heparin-binding protein domain and functions in blood cell migration and apoptosis. Its binding affinity for HA might have been acquired in the vertebrate lineage.     

Role of the FGF and MEK signaling pathway in the ascidian embryo

In the ascidian embryo, a fibroblast growth factor (FGF)-like signal from presumptive endoderm blastomeres between the 32-cell and early 64-cell stages induces the formation of notochord and mesenchyme cells. However, it has not been known whether endogenous FGF signaling is involved in the process. Here it is shown that 64-cell embryos exhibit a marked increase in endogenous extracellular signal-regulated kinase (ERK/MAPK) activity. The increase in ERK activity was reduced by treatment with an FGF receptor 1 inhibitor, SU5402, and a MEK (ERK kinase/MAPKK) inhibitor, U0126. Both drugs blocked the formation of notochord and mesenchyme when embryos were treated at the 32-cell stage, but not at the 2- or 110-cell stages. The dominant-negative form of Ras also suppressed notochord and mesenchyme formation. Both inhibitors suppressed induction by exogenous basic FGF. These results suggest that the FGF signaling cascade is indeed necessary for the formation of notochord and mesenchyme cells during ascidian embryogenesis. It is also shown that FGF signaling is required for formation of the secondary notochord, secondary muscle and neural tissues, and at least ERK activity is necessary for the formation of trunk lateral cells and posterior endoderm. Therefore, FGF and MEK signaling are required for the formation of various tissues in the ascidian embryo.     

RA and FGF Signalling Are Required in the Zebrafish Otic Vesicle to Pattern and Maintain Ventral Otic Identities

During development of the zebrafish inner ear, regional patterning in the ventral half of the otic vesicle establishes zones of gene expression that correspond to neurogenic, sensory and non-neural cell fates. FGF and Retinoic acid (RA) signalling from surrounding tissues are known to have an early role in otic placode induction and otic axial patterning, but how external signalling cues are translated into intrinsic patterning during otic vesicle (OV) stages is not yet understood. FGF and RA signalling pathway members are expressed in and around the OV, suggesting important roles in later patterning or maintenance events. We have analysed the temporal requirement of FGF and RA signalling for otic development at stages after initial anteroposterior patterning has occurred. We show that high level FGF signalling acts to restrict sensory fates, whereas low levels favour sensory hair cell development; in addition, FGF is both required and sufficient to promote the expression of the non-neural marker otx1b in the OV. RA signalling has opposite roles: it promotes sensory fates, and restricts otx1b expression and the development of non-neural fates. This is surprisingly different from the earlier requirement for RA signalling in specification of non-neural fates via tbx1 expression, and highlights the shift in regulation that takes place between otic placode and vesicle stages in zebrafish. Both FGF and RA signalling are required for the development of the otic neurogenic domain and the generation of otic neuroblasts. In addition, our results indicate that FGF and RA signalling act in a feedback loop in the anterior OV, crucial for pattern refinement.     

Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes

Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.     

Signals via FGF receptor 2 regulate migration of endothelial cells.

Fibroblast growth factors (FGFs) stimulate angiogenesis, of which signals are transduced via FGF receptor (FGFR) tyrosine kinases. Although FGFR1 is a major receptor in endothelial cells, FGFR2 is frequently detectable in endothelial cells. We have previously demonstrated that the intracellular domain of FGFR1 sufficiently transduced signals leading to proliferation, migration, urokinase secretion, and tube formation. However, little is known about the roles of signaling via FGFR2 alone in endothelial cells. Murine brain capillary endothelial cells, denoted IBE cells, express small amounts of IIIc FGFR2, which is not activated by keratinocyte growth factor (KGF). We then transfected the IIIb FGFR2 in these cells. Three stable cell lines expressing IIIb FGFR2 demonstrated chemotaxis toward KGF, but never proliferated, secreted urokinase, or formed tube-like structure by KGF treatment. Weak but sustained activation of mitogen-activated protein kinase (MAPK) was observed in these cells. Chemotaxis toward KGF was significantly attenuated by treatment with PD98059. This is the first demonstration that signaling solely via FGFR2 in endothelial cells only contributes to motility through MAPK.     

Assessing the Patterns of Evolution in Anuran Vocal Sexual Signals

Many animal species have evolved signalling traits to mediate various intra-specific interactions. Signals are particularly important for inter-sexual selection, where females use male signalling traits to select mates. Female preferences are therefore a major selective force in the evolution of these male signals, and these preferences can facilitate rapid changes in these traits in an evolutionary timeframe. This introduction of high levels of variation in inter-sexual signals may overshadow any phylogenetic patterns present. Such shadowing effects, however, should be dependant on the characteristics of traits (e.g. morphological, physiological and behavioural). Using male advertisement calls from 72 species of anuran amphibians, we tested the levels of phylogenetic signal present for a variety of call features in relation to trait types, and for calls as whole units using phylogenetic principal components analysis. We found that most call features displayed some level of phylogenetic autocorrelation (or signal), with traits that are dependent on morphology having much stronger phylogenetic signals than those based on behaviour. In addition, when calls were analysed as whole units, closely related species were found to be similar to each other, indicating that phylogenetic patterns had not been cancelled out by selection via female preferences. We suggest that signal functions, such as indicating male quality (e.g. mediated by body size) to potential mates, may place constraints on the amount of variation that can be introduced by female preferences. More research, particularly studies on other taxa, will be required to elucidate whether the patterns found in anurans are general across the animal kingdom.     

成纤维细胞生长因子21对糖脂代谢调控的研究进展

成纤维细胞生长因子21(FGF21)是成纤维细胞生长因子(FGF)家族中的一员。由于它在改善能量代谢方面的积极作用,近年来获得了广泛的关注。FGF21可作用于多个组织参与调控糖脂代谢:减轻体重,改善肥胖、糖尿病等病理情况下的高血糖及高血脂;此外,FGF21在调节饥饿等特殊生理状态的能量代谢中也起着重要的作用。本文就FGF21调控糖脂代谢的研究进展作一综述,以便更好地理解其作用机制,为慢性代谢性疾病的防治提供依据。     

Organization of Actin Filaments and Zonula Adherens during Somitogenesis in the Chick Embryo

The organization of F-actin during somitogenesis in the chick embryo was studied by use of rhodamine-conjugated phalloidin and transmission electron microscopy (TEM). Separation of a somite from the segmental plate proceeded simultaneously with the organization of segmental plate cells into a hemispherical epithelial sheet whose open side was directed antero-laterally. At the same time, intense staining of F-actin appeared in the apical surface of the epithelial sheet. Observations by TEM showed that zonulae adherentes associated with many actin filaments increased in the apical region of cells being organized into an epithelial sheet while this junctional apparatus was only sparsely distributed in the segmental plate cells. The hemispherical sheet subsequently closed to form an epithelial vesicle, with increase in curvature of its apical surface, and narrowing of cellular apices. At the same time, the zonulae adherentes and actin filaments in the cellular apices further increased, and many cellular processes formed on the apical surface of the epithelial somites. These findings suggest that segmentation involves organization of zonulae adherentes and a contractile process caused by acin filaments anchored to the zonulae adherentes.     

A Special Constraint on the Evolution of Composite Signals

Many animals use composite signals, combining e. g. auditory and visual components. If the components travel at different speeds, the time lag between reception of the components increases with increasing distance from the sender. Problems arising especially from rhythmical repetition of composite signals are discussed and possible solutions are indicated.     

Evolution and Diversity of Vibrational Signals in Mantophasmatodea (Insecta)

Vibrational communication for species identification and mate location is widespread among insects. We investigated the vibrational communication signals of 13 species of the insect order Mantophasmatodea (Heelwalkers). Males and females produce percussive signals by tapping their abdomens on the substrate to locate conspecific mates. We show that male and female calls are of similar general structure but differ in temporal characteristics. Using a principal component analysis, we demonstrate that most species can be distinguished by their calls only. Mapping the calls onto an existing molecular phylogenetic tree reveals a slow diverging drift of male call pattern but no specific trend. For females, a trend from faster towards slower pulse repetition times is indicated. Two sympatric species, Karoophasma biedouwense and Viridiphasma clanwilliamense (Austrophasmatidae), exhibit very different call parameters. The latter species produces calls rather different from all other investigated species, which might hint at reproductive character displacement.     

Modeling Sequence-Space Exploration and Emergence of Epistatic Signals in Protein Evolution

During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here, we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous proteins, to propose stochastic models of experimental protein evolution. These models predict quantitatively important features of experimentally evolved sequence libraries, like fitness distributions and position-specific mutational spectra. They also allow us to efficiently simulate sequence libraries for a vast array of combinations of experimental parameters like sequence divergence, selection strength, and library size. We showcase the potential of the approach in reanalyzing two recent experiments to determine protein structure from signals of epistasis emerging in experimental sequence libraries. To be detectable, these signals require sufficiently large and sufficiently diverged libraries. Our modeling framework offers a quantitative explanation for different outcomes of recently published experiments. Furthermore, we can forecast the outcome of time- and resource-intensive evolution experiments, opening thereby a way to computationally optimize experimental protocols.