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PubMed1992

A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain.

The organizer region, or dorsal blastopore lip, plays a central role in the initiation of gastrulation and the formation of the body axis during Xenopus development. A similar process can also be induced in ectodermal explants by activin or by injection of activin mRNA into embryos. We have searched early embryo-specific cDNA libraries for genes containing the fork head box sequence that encodes a DNA-binding domain similar to that of the Drosophila homeotic gene fork head and rat hepatocyte nuclear factor HFN3 beta. These genes were subsequently tested for expression in the organizer region of blastula/gastrula-stage embryos as well as inducibility by activin. Our effort resulted in the isolation of a gene, XFKH1, that is primarily expressed in the dorsal blastopore lip of early gastrulae and is inducible by activin. At later stages it is expressed in the notochord and neural floor plate. Because of its spatial and temporal expression pattern, as well as its inducibility by activin, this gene is a good candidate to have a regulatory function in the initial processes of axis formation in Xenopus laevis embryos.

Activins↗

PubMed1979

Cell number in relation to primary pattern formation in the embryo of Xenopus laevis. II. Sequential cell recruitment, and control of the cell cycle, during mesoderm formation.

Morphological evidence is presented that definitive mesoderm formation in Xenopus is best understood as extending to the end of the neurula phase of development. A process of recruitment of cells from the deep neurectoderm layers into mesodermal position and behaviour, strictly comparable with that already agreed to occur around the internal blastoporal 'lip' during gastrula stage 20 (earliest tail bud). Spatial patterns of incidence of mitosis are described for the fifteen hours of development between the late gastrula and stage 20--22. These are related to the onset of new cell behaviours and overt cyto-differentiations characterizing the dorsal axial pattern, which occur in cranio-caudal and then medio-lateral spatial sequence as development proceeds. A relatively abrupt cessation of mitosis, among hitherto asynchronously cycling cells, precedes the other changes at each level in the presumptive axial pattern. The widespread incidence of cells still in DNA synthesis, anterior to the last mitoses in the posterior-to-anterior developmental sequence of axial tissue, strongly suggests that cells of notochord and somites in their prolonged, non-cycling phase are G2-arrested, and thus tetraploid. This is discussed in relation to what is known of cell-cycle control in other situations. Best estimates for cell-cycle time in the still-dividing, posterior mesoderm of the neurula lie between 10 and 15 h. The supposition of continuing recruitment from neurectoderm can resolve an apparent discrepancy whereby total mesodermal cell number nevertheless contrives to double over a period of approximately 12 h during neurulation when most of the cells are leaving the cycle. Because of pre-existing evidence that cells maintain their relative positions (despite distortion) during the movements that form the mesodermal mantle, the patterns presented in this paper can be understood in two ways: as a temporal sequence of developmental events undergone by individual, posteriorly recruited cells as they achieve their final positions in the body pattern, or alternatively as a succession of wavefronts with respect to changes of cell state, passing obliquely across the presumptive body pattern in antero-posterior direction. These concepts are discussed briefly in relation to recent ideas about pattern formation in growing systems.

Animals↗

PubMed1997

Control of cell-type specific gene expression in Dictyostelium by the general transcription factor GBF.

To understand how positional information within an organism specifies patterning during development, we are analyzing spatially regulated gene expression in Dictyostelium. CAR3 is a member of the cAMP, 7-span receptor family which directs the transition from unicellular to multicellular organism and regulates cellular differentiation and pattern formation. CAR3 mRNA is expressed maximally at 8-10 hours of development, as individual cells aggregate and differentiate, and is accumulated to equivalent levels in all cells. CAR3 is also induced in shaking cultures by response to extracellular cAMP. We now show, by extensive mutagenesis, that the maximum length of contiguous sequences required for accurate spatiotemporal regulation of CAR3 is approx. 350 bp. These sequences include three significant elements located in upstream and transcribed regions. Arrays of G-boxes (GBF regulatory sites) are centered near positions -165 and +50 and, although either is sufficient for induction by cAMP and expression in prespore cells, both are required for expression in prestalk cells. Another GC-rich element near position -80 is required for maximal expression of prespore-specific constructs, although full-length promoters carrying clustered mutations through the -80 region are still expressed in all cells, but with slightly reduced expression. Spatiotemporal expression of CAR3 during development, thus, requires cell-specific combinatorial interactions of multiple but redundant regulatory components. These essential elements are located in upstream and transcribed regions. However, most surprisingly, a primary control for spatial patterning of CAR3 expression appears to be mediated by GBF, a general transcription factor expressed ubiquitously during Dictyostelium development following early aggregation.

Animals↗

PubMed1998

Cellular mechanisms of intestine regeneration in the sea cucumber, Holothuria glaberrima Selenka (Holothuroidea:Echinodermata).

Echinoderms are the deuterostome group with the most striking capacity to regenerate lost body parts. In particular, members of the class Holothuroidea are able to regenerate most of their internal organs following a typical evisceration process. Such formation of new viscera in an adult organism provides a unique model to study the process of organogenesis. We have studied this process in the sea cucumber Holothuria glabberrima by describing the spatial and temporal pattern of cellular events that occur during intestine regeneration following chemically induced evisceration. Regeneration begins as a thickening of the mesenteries that supported the autotomized organs to the body wall. The mesenterial thickening consists of tissues where most of the cellular populations found in the normal intestine are already present. However, the cell numbers differ, particularly those of hemocytes and amoebocytes, suggesting that some of these cells play an important role in the formation of the solid rod of hypertrophic mesentery that characterizes the intestinal primordia. The appearance of the luminal epithelium, together with the formation of the lumen, occurs during the second week of regeneration by proliferation and extensive migration of cells from the esophagus and cloacal ends into the thickenings. At this stage all tissue layers are present, but it takes an additional week for them to exhibit the proportions typical of the normal organ. Cell division, as determined by BrdU labeling, mainly occurs in the coelomic epithelia of the hypertrophic mesentery and in the regenerating luminal epithelium. Our study provides evidence that the process of new organ formation in holothurians can be described as an intermediate process showing characteristics of both epimorphic and morphallactic phenomena.

Animals↗

PubMed2004

Bioconvective pattern formation of Tetrahymena under altered gravity.

Bioconvection is a result of the negative gravitactic behavior of microorganisms. When the top-heavy density gradient generated by gravitaxis grows sufficiently large, an overturning convection occurs leading to a formation of characteristic patterns, which involve highly concentrated aggregation of cells into extended two-dimensional structures. Although gravity is a crucial factor, few experiments have been done with reference to gravity as an experimental variable. In order to gain an insight into the hydrodynamic as well as biological dependence of the convective motion on gravity, we investigated changes in bioconvective patterns of Tetrahymena under altered gravity acceleration generated by a long-arm centrifuge. Bioconvective patterns recorded of three different cell strains (T. pyriformis, T. thermophila and its behavioral mutant, TNR) were analyzed quantitatively using space-time plot and Fourier analysis. For example, under subcritical conditions, when T. pyriformis (1.0 x 10(6) cells ml(-1)) was placed in a 2 mm-deep chamber, no spatial pattern was observed at 1 g. When the suspension was centrifuged, however, patterns began to appear as acceleration increased over a critical value (1.5 g), and then remained steady. The formation was reversible, i.e. the patterns disappeared again as acceleration decreased. Under supracritical conditions, i.e. when a suspension of the same density was placed in a 4 mm-deep chamber, a steady state pattern was formed at 1 g. The pattern spacing in the steady state was observed to decrease stepwise in response to step increases in acceleration. Fourier analysis demonstrated that for TNR the mean wave number changed almost simultaneously with step changes in acceleration, whereas the responses were less sharp in the wild-type strains. This may suggest that the locomotor phenotype of the cell, such as its avoiding response ability, has a crucial role in bioconvective pattern formation. These findings are discussed in relation to former theoretical studies.

Animals↗

PubMed2004

Molecular study of mouse peri-implantation development using the in vitro culture of aggregated inner cell mass.

To study the mechanisms of mouse peri-implantation development, we explored the in vitro culture of the isolated inner cell mass (ICM) of the blastocyst. As previously reported, individually cultured ICM recapitulated several early embryological events, such as the formation of primitive endoderm, epiblast, and proamniotic cavity. However, we found that the timing and efficiency of these morphogenetic processes significantly varied among the ICM. Due to this unpredictability in developmental potential, individually cultured ICM may be unsuitable for further analysis. By contrast, we found that when five ICM were fused into a single mass, such aggregates (5x ICM) underwent efficient and synchronous morphogenesis. The synchronous nature of 5x ICM development was also demonstrated by the temporal and spatial pattern of apoptotic cell death. TUNEL assay showed that a number of the epiblast cells committed apoptosis in 48 hr of culture, which took place after primitive endoderm differentiation but prior to proamniotic cavity formation. In situ hybridization analysis showed that Oct4 was downregulated and alpha-fetoprotein was upregulated in the primitive endoderm of the cultured 5x ICM. In addition, RT-PCR analysis revealed the expression of various primitive endodermal genes, but not of extraembryonic ectodermal markers in the cultured 5x ICM. Taken together, we propose that the 5x ICM is a useful in vitro tool to study the mechanisms of peri-implantation development of the mouse embryo. Mol. Reprod. Dev. 67: 83-90, 2004.

Animals↗

PubMed2005

Complex-ordered patterns in shaken convection.

We report and analyze complex patterns observed in a combination of two standard pattern forming experiments. These exotic states are composed of two distinct spatial scales, each displaying a different temporal dependence. The system is a fluid layer experiencing forcing from both a vertical temperature difference and vertical time-periodic oscillations. Depending on the parameters these forcing mechanisms produce fluid motion with either a harmonic or a subharmonic temporal response. Over a parameter range where these mechanisms have comparable influence the spatial scales associated with both responses are found to coexist, resulting in complex, yet highly ordered patterns. Phase diagrams of this region are reported and criteria to define the patterns as quasiperiodic crystals or superlattices are presented. These complex patterns are found to satisfy four-mode (resonant tetrad) conditions. The qualitative difference between the present formation mechanism and the resonant triads ubiquitously used to explain complex-ordered patterns in other nonequilibrium systems is discussed. The only exception to quantitative agreement between our analysis based on Boussinesq equations and laboratory investigations is found to be the result of breaking spatial symmetry in a small parameter region near onset.

Journal Article↗

PubMed1998

Cell-cell adhesion in limb-formation, estimated from photographs of cell sorting experiments based on a spatial stochastic model.

We developed a new method to estimate the magnitude of differential cell-cell adhesion of two tissues based on the spatial patterns in cell-sorting experiments, and applied it to experimental data on progress-zone cells of avian limb bud at stages 20-26. The change in cell distribution in the experiment was recorded, and statistics qB/B for the degree of cell sorting was calculated from the photographs. Based on extensive computer simulations of spatial Markov processes on a 2-D lattice, we derived a formula for qB/B increasing with time. Using least square fitting, differential adhesion A and cell motility m are estimated from the time series data of qB/B obtained from the experiment. The estimated A was close to 0 (the spatial pattern remained random) if the mixed cells were from two tissues of the same stage. If the mixed cells were from different stages, and the estimated A was positive (cell sorting occurred). Estimated A increased with the difference in the stage number of the two tissues from which the cells were sampled. This result can be explained both by the stage-specific change in adhesion molecules and by a linear increase (or decrease) in the amount of adhesion molecules on cell surface.

Animals↗

PubMed1996

Neuronal control of development in hydra.

Hydra is an excellent model system for developmental biology, because pattern formation processes can be easily studied in regeneration, transplantation, and reaggregation experiments. At the cellular level hydra has the advantage that it contains only a few basic cell types and that differentiation pathways are short. Two types of signals, produced and released by nerve cells, control the spatial and temporal patterns of differentiation. Positive signals induce specific local differentiation events, and negative signals inhibit the spread of such inductions to larger areas. Head-specific growth and differentiation are controlled by head activator and head inhibitor, food-specific processes are regulated by foot activator and foot inhibitor. The activators are peptides, the inhibitors are low-molecular-weight substances. The sequence of the head activator is known, and it is conserved throughout the animal kingdom. At the cellular level head activator exerts three types of effects in hydra. It stimulates cells to divide, and it is responsible for the determination and the final differentiation of nerve cells and head-specific epithelial cells. For nerve-cell differentiation the cAMP pathway is used as second messenger system. Components of this pathway were identified in hydra. In mammals head activator is produced by nerve and neuro-endocrine cells, and it acts as mitogen on cells of neural origin. It is present early in neural development and in abnormal neural development, such as brain and neuroendocrine tumours.

Amino Acid Sequence↗

PubMed1997

Cell death in the developing chick knee joint: I. Spatial and temporal patterns.

The occurrence, distribution and nature of cell death has been studied in the interzone of the developing knee joint of the chick by optical, transmission and scanning electron microscopy. Cell death precedes and accompanies the process of formation of the joint cavity (apart from the femoropatellar component), and is also associated with the surfaces of intra-articular structures as they differentiate within the interzone. Cell death in the knee joint shows many of the morphological characteristics of apoptosis. It is proposed that cell death is one factor in the process of cavity formation in the joint.

Animals↗

PubMed2004

Forest gap dynamics and the Ising model.

The vegetation height in forest ecosystems is spatially heterogeneous. Canopy gaps (sites with low vegetation) are formed by treefalls, and they recover to canopy sites (with high vegetation) either by growth of small trees or by branch extension of surrounding trees. The dynamics of canopy gaps have been studied using a spatial Markov chain with nearest neighbor interaction. (1) If the canopy recovery rate is constant and if the gap formation rate for a site increases exponentially with the number of neighboring gap sites, the equilibrium distribution is the same as the one generated by the Ising model in statistical mechanics. Here, we extend the equivalence to the situation in which both the gap formation and canopy recovery depend on the neighborhood, as shown in recent forest data. (2) We develop a statistical test of whether a given spatial pattern is a random sample from the Ising model. The test is based on the conditional probability of configurations on a partial lattice. We apply the method to vegetation height data from the Ogawa forest reserve, Japan, measured on a 5x5 m grid in 1976, 1981, 1986, and 1991. The spatial pattern of the original forest data deviates significantly from the Ising model. We examine whether a larger sampling distance or the removal of the effects of the topography can reduce this deviation.

Ecosystem↗

PubMed1996

Delayed, selective neuronal death following experimental cortical impact injury in rats: possible role in memory deficits.

Clinical and experimental studies show that loss of neurons in the hippocampus and/or the entorhinal cortex can impede formation and storage of spatial memory. Using a controlled cortical impact model of traumatic brain injury (TBI) in rats, we have examined the temporal and spatial pattern of neuronal death using silver impregnation and cresyl violet staining. Dystrophic neurons can be detected in the dentate gyrus, and the CA1 and CA3 subfields of the hippocampus for up to 2 weeks following injury. These dystrophic cells appeared shrunken and possessed features of apoptosis. Areas containing the dystrophic cells suffer substantial cell loss as demonstrated by thinning of the neuronal layers. Dystrophic cells are also found in the amygdala, entorhinal and piriform cortices, thalamic and hypothalamic regions, and surrounding the contusion site. The loss of these cells may contribute to the memory deficits observed following TBI.

Animals↗

PubMed1998

Adventitial vasa vasorum in balloon-injured coronary arteries: visualization and quantitation by a microscopic three-dimensional computed tomography technique.

OBJECTIVES: The objective of this study was to examine the quantitative response of the adventitial vasa vasorum to balloon-induced coronary injury. BACKGROUND: Recent attention has focused on the role of vasa vasorum in atherosclerotic and restenotic coronary artery disease. However, the three-dimensional anatomy of these complex vessels is largely unknown, especially after angioplasty injury. The purpose of this study was to visualize and quantitate three-dimensional spatial patterns of vasa vasorum in normal and balloon injured porcine coronary arteries. We also studied the spatial growth of vasa vasorum in regions of neointimal formation. A novel imaging technique, microscopic computed tomography, was used for these studies. METHODS: Four pigs were killed 28 d after coronary balloon injury, and four pigs with uninjured coronary arteries served as normal controls. The coronary arteries were injected with a low-viscosity, radiopaque liquid polymer compound. Normal and injured coronary segments were scanned using a microscopic computed tomography technique. Three-dimensional reconstructed maximum intensity projection and voxel gradient shading images were displayed at different angles and voxel threshold values, using image analysis software. For quantitation, seven to 10 cross-sectional images (40 normal and 32 balloon injured cross-sections) were captured from each specimen at a voxel size of 21 microm. RESULTS: Normal vasa vasorum originated from the coronary artery lumen, principally at large branch points. Two different types of vasa were found and classified as first-order or second-order according to location and direction. In balloon-injured coronary arteries, adventitial vasa vasorum density was increased (3.16+/-0.17/mm2 vs. 1.90+/-0.06/mm2, p = 0.0001; respectively), suggesting neovascularization by 28 d after vessel injury. Also, in these injured arteries, the vasa spatial distribution was disrupted compared with normal vessels, with proportionally more second-order vasa vasorum. The diameters of first-order and second-order vasa were smaller in normal compared with balloon-treated coronary arteries (p = 0.012 first-order; p < 0.001, second-order; respectively). The density of newly formed vasa vasorum was proportional to vessel stenosis (r = 0.81, p = 0.0001). Although the total number of vasa was increased after injury, the total vascular area comprised of vasa was significantly reduced in injured vessels compared with normals (3.83+/-0.20% to 5.42+/-0.56%, p = 0.0185). CONCLUSIONS: Adventitial neovascularization occurs after balloon injury. The number of new vessels is proportional to vessel stenosis. These findings may hold substantial implications for the therapy of vascular disease and restenosis.

Angioplasty, Balloon, Coronary↗

PubMed2006

Temporal and spatial pattern of embolism induced by pressure collar techniques in twigs of Picea abies.

The pressure collar technique enables the induction of embolism in plant xylem. This artificial cavitation is based on air seeding processes which occur when specific pressure gradients between the air and water phase of the xylem are exceeded. Standard pressure collars and a new point injection technique, which builds up a local potential gradient, were used to study the time and spatial pattern of this process. On twigs of Norway spruce (Picea abies), the cross-sectional and axial pattern, and the time-course of embolism formation were analysed via conductivity and ultrasonic measurements as well as staining experiments. Furthermore, the release of air from the twig surface was studied by immersing twig sections in water. In cross-sections, embolized areas induced by the point injection technique were smaller compared with the standard collar and restricted to a circle sector. Embolism propagated from the pressure collar towards the nearest distal and proximal nodes but not further. A release of air was also observed predominantly at the internode attached to the pressure collar. Embolism rates increased within minutes and reached approximately 80% loss of conductivity after 10 min treatment with the standard collar. The size of air entry points and embolism rates correlated significantly. Embolism formation in wood therefore depends not only on vulnerability thresholds but also on the extent of air-water interfaces within the xylem and on the time of exposure to pressure gradients. These aspects and the propagation of pressure within samples are crucial for pressure collar experiments. In addition, wood architecture influences the extent and pattern of embolism caused by air seeding processes.

Air↗

PubMed1989

Spatial patterns from oscillating microtubules.

Microtubules are fibers of the cytoskeleton involved in the generation of cell shape and motility. They can be highly dynamic and are capable of temporal oscillations in their state of assembly. Solutions of tubulin (the subunit protein of microtubules) and guanosine triphosphate (GTP, the cofactor required for microtubule assembly and oscillations) can generate various dissipative structures. They include traveling waves of microtubule assembly and disassembly as well as polygonal networks. The results imply that cytoskeletal proteins can form dynamic spatial structures by themselves, even in the absence of cellular organizing centers. Thus the microtubule system could serve as a simple model for studying pattern formation by biomolecules in vitro.

Biopolymers↗

PubMed2005

GIS and epidemiology.

Understanding the spatial patterns of infectious diseases can provide insight as to their causes and controls. Geographic information systems (GIS) and related technologies like remote sensing are increasingly used to analyze geographical distribution of diseases as well as relationships between pathogenic factors (causative agents, patients, vectors and hosts) and their geographic environments. Basic and analytical applications of GIS in epidemiology can help in visualizing and analyzing geographic distribution of diseases through time, thus revealing spatio-temporal trends, patterns, and relationships that would be more difficult or obscure to discover in tabular or other formats. GIS can provide a means to meet the demands of outbreak investigation and response, where understanding the spatial spread and dynamics of an outbreak is central to the design of prevention and control strategies.

Communicable Diseases↗

PubMed2003

Source profiles and ozone formation potentials of volatile organic compounds in three traffic tunnels in Kaohsiung, Taiwan.

Twenty-five volatile organic compounds (VOCs) up to C10 were measured using Carbotrap multibed thermal adsorption tubes during the morning and afternoon rush hours on four different days in all three traffic tunnels in Kaohsiung, Taiwan. A gas chromatograph (GC) equipped with a flame-ionization detector (FID) was then used to analyze the VOCs. The analytical results show that VOC concentrations increase with traffic flow rate, and emission profiles in the three tunnels are mostly in the range C2-C6. In addition to the traffic conditions and vehicle type, the pattern of emissions in each tunnel was also influenced by other factors, such as vehicle age, nearby pollution sources, and the spatial or temporal variation of VOCs in the urban atmosphere. The ozone formation potential (OFP) in each tunnel was assessed based on the maximum incremental reactivities of the organic species, demonstrating that OFP increases with traffic flow rate. Vehicle distribution influences the contributions of organic group to OFP in a tunnel. Meanwhile, when ranked in descending order of contribution to OFP in all tunnels, the organic groups followed the sequence olefins, aromatics, and paraffins.

Air Pollutants↗

PubMed2000

Progressive segregation of unmyelinated axons in peripheral nerves, myelin alterations in the CNS, and cyst formation in the kidneys of myelin and lymphocyte protein-overexpressing mice.

Myelin and lymphocyte protein (MAL) is a putative tetraspan proteolipid that is highly expressed by Schwann cells and oligodendrocytes as a component of compact myelin. Outside of the nervous system, MAL is found in apical membranes of epithelial cells, mainly in the kidney and stomach. Because MAL is associated with glycosphingolipids, it is thought to be involved in the organization, transport, and maintenance of glycosphingolipid-enriched membrane microdomains. In this report, we describe the generation and analysis of transgenic mice with increased MAL gene dosage. Immunohistochemical analysis revealed that the localization of MAL overexpression in the transgenic animals corresponded closely to the MAL expression pattern observed in wildtype animals, indicating correct spatial regulation of the transgene. Phenotypically, MAL overexpression led to progressive dissociation of unmyelinated axons from bundles in the PNS, a tendency to hypomyelination and aberrant myelin formation in the CNS, and the formation of large cysts in the tubular region of the kidney. Thus, increased expression of MAL appears to be deleterious to membranous structures in the affected tissues, indicating a requirement for tight control of endogenous MAL expression in Schwann cells, oligodendrocytes, and kidney epithelial cells.

Abnormalities, Multiple↗