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PubMed2001

Novel VEGF family members: VEGF-B, VEGF-C and VEGF-D.

Vascular endothelial growth factors (VEGFs) constitute a group of structurally and functionally related growth factors that modulate many important physiological functions of endothelial cells. Currently, five different mammalian VEGFs have been identified and they all show unique temporal and spatial expression patterns, receptor specificity and function. The VEGFs may play pivotal roles in formation of the vascular systems during embryonic development, in regulation of capillary growth in normal and pathological conditions in adults, and in the maintenance of the normal vasculature. In the future, the VEGFs and their receptors may become important therapeutic tools in treatment of conditions characterized by aberrant or defective formation of blood vessels and lymphatic vessels.

Animals↗
PubMed2004

A photolabile hydrogel for guided three-dimensional cell growth and migration.

Tissue engineering aims to replace, repair or regenerate tissue/organ function, by delivering signalling molecules and cells on a three-dimensional (3D) biomaterials scaffold that supports cell infiltration and tissue organization. To control cell behaviour and ultimately induce structural and functional tissue formation on surfaces, planar substrates have been patterned with adhesion signals that mimic the spatial cues to guide cell attachment and function. The objective of this study is to create biochemical channels in 3D hydrogel matrices for guided axonal growth. An agarose hydrogel modified with a cysteine compound containing a sulphydryl protecting group provides a photolabile substrate that can be patterned with biochemical cues. In this transparent hydrogel we immobilized the adhesive fibronectin peptide fragment, glycine-arginine-glycine-aspartic acid-serine (GRGDS), in selected volumes of the matrix using a focused laser. We verified in vitro the guidance effects of GRGDS oligopeptide-modified channels on the 3D cell migration and neurite outgrowth. This method for immobilizing biomolecules in 3D matrices can generally be applied to any optically clear hydrogel, offering a solution to construct scaffolds with programmed spatial features for tissue engineering applications.

Animals↗
PubMed2004

The long-term stability of new hippocampal place fields requires new protein synthesis.

The hippocampus is critical for formation of spatial memories. Hippocampal pyramidal neurons in freely behaving animals exhibit spatially selective firing patterns, which taken together form an internal representation of the environment. This representation is thought to contribute to the hippocampal spatial memory system. Behavioral long-term memories differ from short-term memories in requiring the synthesis of new proteins. Does the development of the internal hippocampal representation also require the synthesis of new proteins? We found that blocking protein synthesis in the brain of mice by 95% does not affect short-term stability of newly formed hippocampal place fields but abolishes stability in the long term. By contrast, inhibiting protein synthesis does not affect the retention and recall of previously established fields in a familiar environment, indicating that protein synthesis-dependent reconsolidation is not required for recall. Our results indicate that place fields parallel both behavioral memories and the late phase of long-term potentiation in requiring the synthesis of new proteins for consolidation.

Action Potentials↗
PubMed2006

Historical processes enhance patterns of diversity along latitudinal gradients.

One of the more vexing issues in ecology is how historical processes affect contemporary patterns of biodiversity. Accordingly, few models have been presented. Two corollary models (centre of origin, time-for-speciation) can be used to make quantitative predictions characterizing the tropical niche conservatism hypothesis and describe diversification as diffusion and subsequent cladogenesis of species away from the place of origin of a higher taxon in the tropics. Predictions derived from such models are: (i) species richness declines toward the periphery of the range of a higher taxon; (ii) taxa are more derived toward the periphery than the centre; (iii) ages of taxa are lower toward the periphery than the centre; and (iv) ages and measures of derivedness are less variable toward the periphery of the range of a higher taxon. I tested these predictions to better understand the formation of one of the most ubiquitous patterns of biodiversity-the latitudinal gradient in species richness. Results indicate well-supported predictions for New World leaf-nosed bats and that diversification has had strong influences on latitudinal gradients of species richness. A better understanding of how evolutionary diversification of taxa contributes to formation of patterns of species richness along environmental gradients is necessary to fully understand spatial variation in biodiversity.

Animals↗
PubMed1996

Regulation and function of the terminal gap gene huckebein in the Drosophila blastoderm.

Pattern formation in Drosophila involves a cascade of maternal and zygotic factors which are spatially restricted in the blastoderm embryo. Here we show that the Drosophila gene huckebein (hkb), a member of the gap gene class of segmentation genes, is not only required for suppression of segmentation in the terminal regions of the embryo but also to spatially restrict germ layer formation at the beginning of gastrulation. hkb encodes a Sp1/egr-like zinc finger protein, likely to be a transcription factor. Its absence in hkb mutants causes the ectodermal and mesodermal primordia to expand at the expense of endoderm anlagen, which are completely absent in null alleles of hkb. Conversely, ectopic expression of hkb inhibits the formation of the major gastrulation fold which gives rise to the mesoderm and prevents normal segmentation in the ectoderm of the trunk region.

Animals↗
PubMed2000

Galanin and spatial learning in the rat. Evidence for a differential role for galanin in subregions of the hippocampal formation.

Anatomical, neurochemical and behavioural evidence support a role for galanin in hippocampally mediated functions such as spatial learning and memory. To obtain more precise information on this role, galanin (3 nmol/rat) was infused via bilateral chronic cannulae into different areas of the hippocampal formation which are characterized by different galanin receptor subtypes and also by different galanin innervation patterns. The effects of infused galanin on spatial learning were examined in the Morris swim maze. Infusions of galanin into both the dorsal and ventral dentate gyrus, which mainly contain GAL-R2 receptor mRNA and a high degree of galanin-noradrenaline coexistence, significantly retarded spatial acquisition without affecting swim speed or performance in the visible platform test. This spatial learning deficit was fully blocked by pretreatment with the non-selective galanin antagonist M35. Analysis of retention performance suggested that the major effect of intrahippocampal galanin is mediated via a specific disruption of acquisition mechanisms of importance for performance in the probe trial. Galanin infused into the ventral CA1 (a mainly GAL-R1 receptor mRNA expressing region) or into anterior, ventral CA3 regions did not produce any deficits in spatial learning compared to control animals. These results suggest that galanin mediates its action on spatial learning mainly through the GAL-R2 receptor subtype in areas where most of the galanin is present in noradrenergic terminals. A possible role for the GAL-R1 receptor subtype in cognition in the dorsal and ventral hippocampus remains to be defined. The results suggest a differential functional role for galanin and galanin receptor subtypes within subregions of the hippocampal formation.

Animals↗
PubMed1996

Neural cell pattern formation on glass and oxidized silicon surfaces modified with poly(N-isopropylacrylamide).

Control over the adsorption of proteins and over the adsorption and spatial orientation of mammalian cells onto surfaces has been achieved by modification of glass and other silicon oxide substrates with poly(N-isopropylacrylamide) (PNIPAM). The functionalization of the substrates was achieved either by a polymer-analogous reaction of aminosilanes with reactive N-(isopropylacrylamide) (NIPAM)-copolymers and by copolymerization of NIPAM with surface-bound methacrylsilane. The obtained coatings were characterized by FT-1R, ellipsometry, and surface plasmon resonance measurements. The adsorption of two proteins-fibrinogen and ribonuclease A-on these surfaces was studied in situ by real time surface plasmon resonance measurements. The PNIPAM-grafted surfaces prepared by either chemical procedure inhibited the adsorption of both proteins. More importantly they prevented the adhesion of neuroblastomaXglioma hybrid cells cultured either in serum-free medium or in a medium containing serum proteins. Deep-UV irradiation was used to perform ablation processes and to create patterns permitting the examination of spatially controlled adhesion and growth of cells. This study showed that patterned ultrathin polymer films on glass are suitable substrates for controlling the interactions of cells with surfaces and are capable of directing the attachment and spreading of cells.

Acrylamides↗
PubMed2006

Retinoids, eye development, and maturation of visual function.

Vitamin A is known to be critical for the beginning of eye development as well as for photoreception in the functional retina. Hardly anything, however, is known about whether retinoic acid (RA)-regulated gene expression also plays a role in the long intervening period, during which the neurobiological retinal structure takes shape. The eye contains a highly intricate architecture of RA-synthesizing (RALDH) and degrading (CYP26) enzymes. Whereas the RALDHs are integrated in the early molecular mechanisms through which the dorso-ventral retina organization is established, the CYP26 enzymes are not necessary for this process and no molecular targets that match their retinal expression pattern have yet been identified. In this article we describe that CYP26 expression in the mouse is most distinctive during later stages of retina formation. Throughout development CYP26A1 degrades RA in a horizontal region that extends across the retina, but during later embryonic and postnatal retina maturation this function is reinforced by another enzyme, CYP26C1. RA applications at this stage do not affect the RALDHs but cause differential changes in CYP26 expression: Cyp26a1 is up-regulated, but more rapidly by 9-cis than all-trans RA, Cyp26c1 is down-regulated, and Cyp26b1, which is undetectable in the normal mouse retina, is strongly activated in retinal ganglion cells. The dynamic regulation in RA-difference patterns by the CYP26 enzymes may set up spatial constellations for expression of genes involved in formation of retinal specializations for higher acuity vision, which are known to form over a prolonged period late in retina development.

Aldehyde Oxidoreductases↗
PubMed2000

Measurement of the spatial coherence of a trapped Bose gas at the phase transition

The experimental realization of Bose-Einstein condensates of dilute gases has allowed investigations of fundamental concepts in quantum mechanics at ultra-low temperatures, such as wave-like behaviour and interference phenomena. The formation of an interference pattern depends fundamentally on the phase coherence of a system; the latter may be quantified by the spatial correlation function. Phase coherence over a long range is the essential factor underlying Bose-Einstein condensation and related macroscopic quantum phenomena, such as superconductivity and superfluidity. Here we report a direct measurement of the phase coherence properties of a weakly interacting Bose gas of rubidium atoms. Effectively, we create a double slit for magnetically trapped atoms using a radio wave field with two frequency components. The correlation function of the system is determined by evaluating the interference pattern of two matter waves originating from the spatially separated 'slit' regions of the trapped gas. Above the critical temperature for Bose-Einstein condensation, the correlation function shows a rapid gaussian decay, as expected for a thermal gas. Below the critical temperature, the correlation function has a different shape: a slow decay towards a plateau is observed, indicating the long-range phase coherence of the condensate fraction.

Journal Article↗
PubMed2004

[Geostatistics analyzing to cause of formation of circle distribution of plant communities in Horqin Sandy Land].

Investigation results in the present study showed that plant communities took typical concentric circles distribution patterns along habitat gradient from top, slope to interdune on a few large fixed dunes in middle part of Korqin Sandy Land. In order to explain this phenomenon, analysis of water content and its spatial heterogeneity in sand layers on different locations of dunes was conducted. In these dunes, water contents in sand layers of the tops were lower than those of the slopes; both of them were lower than those of the interdunes. According to the results of geostatistics analysis, whether shifting dune or fixed dune, spatial heterogeneity of water contents in sand layers took on regular changes, such as ratios between nugget and sill and ranges reduced gradually, fractal dimension increased gradually, the regular changes of these parameters indicated that random spatial heterogeneity reduced gradually, and autocorrelation spatial heterogeneity increased gradually from the top, the slope to the interdune. The regular changes of water contents in sand layers and their spatial heterogeneity of different locations of the dunes, thus, might be an important cause resulted in the formation of the concentric circles patterns of the plant communities on these fixed dunes.

China↗
PubMed2001

Domain coexistence in nonlinear optical pattern formation.

We report on domain coexistence of a variety of different modes in a two-dimensional nonlinear optoelectronic model. The changes of stabilities of these modes are shown to give rise to new forms of spatial and spatiotemporal structures. The existence of these domain patterns explains some of the patterns recently observed in an optical system with a large array optoelectronic feedback circuit.

Journal Article↗
PubMed1990

Morphogenesis of precursor subpopulations of chicken limb mesenchyme in three dimensional collagen gel culture.

Although homogeneous in appearance, several lines of evidence suggest early (stage 17-19) limb mesenchymal cells are committed to particular cell lineages, e.g., myogenic or chondrogenic. However, subsequent expression of cell or tissue phenotype in the developing limb does not occur in a randomized process but rather in a spatially specific pattern. The potential regulatory mechanisms controlling the "patterned" expression of tissue phenotype in the limb have not been resolved. The purpose of this study was to determine if, prior to the formation of an apical ectodermal ridge, nondissociated limb mesenchyme has inherent morphogenetic potential to form nonrandomized patterns of tissue organization. The hypotheses to be tested were that, if provided a spatially permissive culture environment, 1) mesenchymal cells committed to a particular lineage would segregate into precursor (sub)populations prior to overt expression of phenotype and 2) the ultimate expression of a tissue phenotype may be regulated, in part, by histogenic interactions between the precursor cell groups. For these studies, mesoblasts (intact mesenchyme minus ectoderm) from stage 17-19 hindlimb buds were explanted intact to the surface of a 1-3 mm thick hydrated lattice of repolymerized type I collagen and incubated for 2-11 days. Examination of cultures at variable intervals revealed three distinct temporal sequences (periods) which were arbitrarily termed early morphogenesis (0-3 days), cytodifferentiation (3-5.5 days), and primitive tissue formation (5.5-11 days) based on similarities to in situ limb development. By the end of the first period, the mesenchymal cells had sorted into three distinct precursor populations: 1) an epithelial-like outgrowth of premyogenic and prefibrogenic cells at the surface of the gel lattice (termed the "surface subset") which circumscribed, 2) a centrally positioned prechondrogenic condensate ("central subset"), and overlaid 3) a dispersed, population of free cells that invaded the collagen lattice ("seeded subset"). Subsequent cytodifferentiation led to the appearance of multinucleated myotubes within the surface subset and chondrification of the central subset. Cells of the seeded subset remained dispersed within the collagen lattice. Primitive histogenic events were initiated during the final period of development including 1) at sites where surface cells established boundaries with the central subset, collectives or "bundles" of variable sized myotubes were formed which became partially ensheathed by the attenuated processes of fibroblastlike cells; and 2) a secondary site of chondrogenic activity was initiated within the gel lattice at the boundary between the central and seeded cell populations. Transformation of seeded fibroblasts into chondroblasts accompanied expansion of the secondary chondrogenic element within the gel lattice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

Organizer and axes formation as a self-organizing process.

It is a widely held view that axis formation is based essentially on pre-localized determinants. However, the robustness of early development, the pattern regulation observed after experimental interferences and the existence of systems that don't require maternal determinants suggest that self-regulating pattern forming systems are also involved. A model is proposed that allows axes formation by a chain of reactions based on local self-enhancement and long-range inhibition. Their appropriate linkage ensures that the intermediary patterns emerge in the correct sequence and have the correct spatial relation to each other. Specifically, the model comprises the following events: the generation of a pole by a pattern-forming process, the formation of a second organizer eccentric to the pole (e.g. the Nieuwkoop center), the ecto-meso-endo subdivision, the generation of the Spemann-Mangold organizer with its anterior-posterior subdivision under the influence of the Nieuwkoop center, the conversion of the Spemann-Mangold organizer (a hot spot) into the notochord (a hot stripe), and the marking of the left side of the organism by a patterning reaction influenced by the midline. The pattern forming reactions do not depend on but can make use of maternally pre-localized determinants or asymmetries. Comparison with known genes and molecules reveals that many of the expected ingredients are present. Computer simulations show that the model accounts for many regulatory features reported in the literature. The computer simulations are available in an animated form at.

Animals↗
PubMed2005

Spatial periodicity of Escherichia coli K-12 biofilm microstructure initiates during a reversible, polar attachment phase of development and requires the polysaccharide adhesin PGA.

Using fast Fourier transform (FFT) analysis, we previously observed that cells within Escherichia coli biofilm are organized in nonrandom or periodic spatial patterns. Here, we developed a gravity displacement assay for examining cell adherence and used it to quantitatively monitor the formation of two distinct forms of cell attachment, temporary and permanent, during early biofilm development. Temporarily attached cells were mainly surface associated by a cell pole; permanent attachments were via the lateral cell surface. While temporary attachment precedes permanent attachment, both forms can coexist in a population. Exposure of attached cells to gravity liberated an unattached population capable of rapidly reassembling a new monolayer, composed of temporarily attached cells, and possessing periodicity. A csrA mutant, which forms biofilm more vigorously than its wild-type parent, exhibited an increased proportion of permanently attached cells and a form of attachment that was not apparent in the parent strain, permanent polar attachment. Nevertheless, it formed periodic attachment patterns. In contrast, biofilm mutants with altered lipopolysaccharide synthesis (waaG) exhibited increased cell-cell interactions, bypassed the polar attachment step, and produced FFT spectra characteristic of aperiodic cell distribution. Mutants lacking the polysaccharide adhesin beta-1,6-N-acetyl-d-glucosamine (DeltapgaC) also exhibited aperiodic cell distribution, but without apparent cell-cell interactions, and were defective in forming permanent attachments. Thus, spatial periodicity of biofilm microstructure is genetically determined and evident during the formation of temporary cell surface attachments.

Adhesins, Bacterial↗
PubMed1997

The Na+,K+-ATPase alpha subunit requires gastrulation in the Xenopus embryo.

Na+,K+-ATPase participates in reabsorption of ions and water and produces an electrochemical gradient between the intra- and extracellular spaces across the cell membrane. It also plays an important role in many developmental phenomena such as a blastocoele formation and neural formation. To elucidate the expression pattern of Na+,K+-ATPase in the Xenopus embryo, the spatial expression patterns of the Na+,K+-ATPase alpha subunit were studied in a normal embryo by whole-mount in situ hybridization. These transcripts were localized around the dorsal blastopore at the gastrula stage, in the neural tube at the neurula stage, and then in the pronephros and cloaca at the tail-bud stage. To study the function of Na+,K+-ATPase in embryogenesis after mid-blastula transition, the expression of the Na+,K+-ATPase alpha subunit was inhibited by the injection of specific antisense RNA. Embryos injected with Na+,K+-ATPase antisense RNA showed inhibition of gastrulation. When antisense RNA was injected into the dorsal blastomeres, head differentiation was markedly inhibited. These results suggest that this transcript plays an important role during gastrulation and head differentiation.

Activins↗
PubMed2003

The receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenic pathway is elevated in amelogenin-null mice.

Amelogenins, major components of developing enamel, are predominantly involved in the formation of tooth enamel. Although amelogenins are also implicated in cementogenesis, their precise spatial expression pattern and molecular role are not clearly understood. Here, we report for the first time the expression of two alternate splice forms of amelogenins, M180 and the leucine-rich amelogenin peptide (LRAP), in the periodontal region of mouse tooth roots. Lack of M180 and LRAP mRNA expression correlated with cementum defects observed in the amelogenin-null mice. The cementum defects were characterized by an increased presence of multinucleated cells, osteoclasts, and cementicles. These defects were associated with an increased expression of the receptor activator of the nuclear factor-kappa B ligand (RANKL), a critical regulator of osteoclastogenesis. These findings indicate that the amelogenin splice variants, M180 and LRAP, are critical in preventing abnormal resorption of cementum.

Alternative Splicing↗
PubMed1989

Characterization of epithelial domains in the nasal passages of chick embryos: spatial and temporal mapping of a range of extracellular matrix and cell surface molecules during development of the nasal placode.

The formation of the nasal passages involves complex morphogenesis and their lining develops a spatially ordered pattern of differentiation, with distinct domains of olfactory and respiratory epithelium. Using antibodies to the neural cell adhesion molecule (N-CAM), keratan sulphate and heparan sulphate proteoglycan (HSPG) and a panel of lectins (agglutinins of Canavalia ensiformis (ConA), Dolichos biflorus (DBA), peanut (PNA), Ricinis communis (RCA1), soybean (SBA), Ulex europaeus (UEA1), and wheatgerm (WGA], we have documented cell surface characteristics of each epithelial domain. Binding of antibodies to N-CAM and to keratan sulphate, and the lectins ConA, PNA, RCA1, SBA and WGA marks the olfactory epithelial domain only. The restriction of N-CAM to the sensory region of the epithelium has also been reported in the developing ear. This striking similarity is consistent with the idea that N-CAM may be involved in the division of functionally and histologically distinct cell groups within an epithelium. We traced the olfactory-specific cell markers during development to gain insights into the origin of the epithelial lining of the nasal passages. All reagents bind at early stages to the thickened nasal placode and surrounding head ectoderm and then become progressively restricted to the olfactory domain. The expression of these characteristics appears to be modulated during development rather than being cell autonomous. The distribution of keratan sulphate was compared with collagen type II in relation to the specification of the chondrocranium. Keratan sulphate and collagen type II are only colocalized at the epithelial-mesenchymal interface during early nasal development. At later stages, only collagen type II is expressed at the interface throughout the nasal passages, whereas keratan sulphate is absent beneath the respiratory epithelium.

Animals↗