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Temporal and spatial expression of the myostatin gene during chicken embryo development.

Myostatin is a potent growth and differentiation factor involved in skeletal muscle tissue formation in vertebrates. In the present study, temporal and spatial expression patterns of myostatin transcripts were investigated in chicken embryos. Myostatin mRNA was detected by RT-PCR analysis in embryos collected immediately after oviposition (stage HH1) and persisted until the fifth day of incubation (stage HH26). Whole-mount in situ hybridization revealed myostatin to be expressed in the ventral myotomal region of mature somites, thus confirming the importance of myostatin in skeletal muscle tissue formation during avian embryogenesis. A smaller myostatin transcript was also identified. This transcript appears to have resulted from an alternative splicing event from common GT-AG processing sites. Analysis of the amino acid sequence generated from this alternative transcript confirmed the presence of a truncated protein that lacks the C terminal region, including the cysteine domains characteristic of the TGF-beta super family. The temporal and spatial patterns of myostatin expression presented in this study agree with the proposed role of myostatin as modulator of muscle cell proliferation.

Alternative Splicing↗

Microtubule distribution in dv, a maize meiotic mutant defective in the prophase to metaphase transition.

Microsporogenesis in Zea mays, the meiotic reduction of diploid sporocytes to haploid microspores, proceeds through a well-defined developmental sequence. The ability to generate mutants that affect the process makes this an ideal system for elucidating the role of the cytoskeleton during plant development. We have used immunofluorescence microscopy to compare microtubule distribution in wild-type and mutant microsporocytes. During normal meiosis the distribution of microtubules follows a specific temporal and spatial pattern that reflects the polar nature of microspore formation. Perinuclear microtubule staining increases and the nucleus elongates in the future spindle axis during late prophase I. Metaphase I spindles with highly focused poles align along the long axis of the anther locule. Cytokinesis occurs perpendicular to the spindle axis. The second division axis shifts 90 degrees with respect to the first division plane, thereby yielding an isobilateral tetrad of microspores. Microtubule distribution patterns during meiosis suggest that a nuclear envelope-associated microtubule organizing center (MTOC) controls the organization of cytoplasmic microtubules and contributes to spindle formation. The meiotic mutant dv is defective in the transition from a prophase microtubule array to a metaphase spindle. Instead of converging to form focused poles, the metaphase spindle poles remain diffuse as in prometaphase. This defect correlates with several abnormalities in subsequent developmental events including the formation of multinucleate daughter cells, multiple microspindles during meiosis II, multiple phragmoplasts, polyads of microspores, and cytoplasmic microtubule foci. These results suggest that dv is a mutation that affects MTOC organization.

Cell Division↗

Sequential distribution of keratan sulphate and chondroitin sulphate epitopes during ameloblast differentiation.

Proteoglycans are complex macromolecules containing one or more glycosaminoglycan chains and exhibiting a variety of biological functions in connective tissues. The aim of the present study was to immunolocalize the distribution of keratan sulphate and chondroitin sulphate epitopes during initial enamel formation in order to study temporo-spatial expression patterns of these macromolecules. Third molars of four-months-old pigs were used for immunolocalization of keratan sulphate and chondroitin sulphate epitopes in the developing enamel layer. Tooth organs were prepared for paraffin sections in order to perform indirect immunohistochemistry. The results demonstrated a mutually exclusive positioning between these two epitopes. Keratan sulphate epitopes were observed in pre-secretory pre-ameloblasts and adjacent stratum intermedium while chondroitin sulphate epitopes were demonstrated in secretory ameloblasts and adjacent stratum intermedium. Our findings suggest that proteoglycans containing glycosaminoglycan chains may play a regulatory role during enamel mineralization.

Ameloblasts↗

Competition of periodic and homogeneous modes in extended dynamical systems.

Despite their simple structure, spatially homogeneous modes can participate directly in pattern-formation processes. This is demonstrated by new experimental and theoretical results for thermo- and electroconvection in planar nematic liquid crystals, where two distinct homogeneous modes, twist and splay distortions of the director field, emerge. Their nonlinear excitation is due to certain spontaneous symmetry-breaking bifurcations.

Journal Article↗

Ectopic Hoxa-1 induces rhombomere transformation in mouse hindbrain.

Homeobox genes are expressed with a specific spatial and temporal order, which is essential for pattern formation during the early development of both invertebrates and vertebrates. Here we show that widespread ectopic expression of the Hoxa-1 (Hox 1.6) gene directed by a human beta-actin promoter in transgenic mice is embryolethal and produces abnormal phenotypes in a subset of domains primarily located in anterior regions. Interestingly, this abnormal development in the Hoxa-1 transgenic mice is associated with ectopic expression of the Hoxb-1 (Hox 2.9) gene in select hindbrain regions. At gestation day 9.5, two domains of strong Hoxb-1 expression are found in the anterior region of the hindbrains of Hoxa-1 transgenic embryos. One region represents the normal pattern of Hoxb-1 expression in rhombomere 4 and its associated migrating neural crest cells, while another major domain of Hoxb-1 expression consistently appears in rhombomere 2. Similar ectopic domains of beta-galactosidase activity are detected in dual transgenic embryos containing both beta-actin/Hoxa-1 transgene and a Hoxb-1/lacZ reporter construct. Expression of another lacZ reporter gene that directs beta-galactosidase activity predominantly in rhombomere 2 is suppressed in the Hoxa-1 transgenic embryos. We have also detected weaker and variable ectopic Hoxb-1 expression in rhombomeres 1, 3 and 6. No ectopic Hoxb-1 expression is detected in rhombomere 5 and the expression of Hoxa-3 and Krox-20 in this region is unchanged in the Hoxa-1 transgenic embryos. While no obvious change in the morphology of the trigeminal or facial-acoustic ganglia is evident, phenotypic changes do occur in neurons that emanate from rhombomeres 2 and 3 in the Hoxa-1 transgenic embryos. Additionally, alterations in the pattern of Hoxa-2 and Hoxb-1 expression in a subpopulation of neural crest cells migrating from the rhombomere 2 region are detected in these transgenics. Taken together, these data suggest that ectopic Hoxa-1 expression can reorganize select regions of the developing hindbrain by inducing partial transformations of several rhombomeres into a rhombomere-4-like identity.

Actins↗

Prominence of direct entorhinal-CA1 pathway activation in sensorimotor and cognitive tasks revealed by 2-DG functional mapping in nonhuman primate.

The trisynaptic pathway from entorhinal cortex to the hippocampus has long been regarded as the major route of information transfer underlying memory consolidation. Most physiological studies of this pathway involve recording from hippocampal slices. We have used both single- and double-label 2-deoxyglucose autoradiographic methods to image the pattern of activation in the hippocampal formation of 14 rhesus monkeys performing cognitive tasks, varying in content (spatial or nonspatial), process (working memory or associative memory), and mode of response (oculomotor or manual). These studies revealed a highly differentiated pattern of metabolic activation throughout the rostrocaudal extent of the hippocampal formation that was common to all behavioral conditions examined. This pattern consisted of intense activation of the stratum lacunosum-moleculare of CA1 and the subiculum, contrasting with barely detectable activity in CA3 and modest activation in the dentate gyrus, which did not include its molecular layer. These findings indicate a remarkable invariance in hippocampal activation under conditions of varied content, varied process, and varied mode of response and an heretofore-unappreciated preferential engagement of the direct rather than the trisynaptic pathway during performance of a wide range of behavioral tasks.

Animals↗

[Formation of the regular, optical isotropic phase of low molecular weight DNA molecules modified by cis-dichlorodiammineplatinum].

It is shown that condensation of DNA molecules of low molecular mass (less than 1 X 10(6) in NaClO4-containing solution of poly(ethylene glycol) brings about formation of cholesteric liquid crystal phase; pattern of this phase is presented. It has been found by means of X-ray analysis and polarization microscopy that at certain level of modification with cis-dichlorodiammineplatinum (II) the DNA molecules instead of cholesteric structure form an ordered optically isotropic phase. The problem about the causes of the formation of such phase and about the pattern of spatial organisation of adjacent DNA molecules in it remains open.

Animals↗

Potential role of Sox9 in patterning tracheal cartilage ring formation in an embryonic mouse model.

OBJECTIVE: To identify genes expressed early in the formation of the mouse trachea that control patterning of tracheal cartilaginous rings. DESIGN: The mouse larynx and trachea begin as an outpouching from the ventral foregut endoderm at embryonic day (E) 9. Digoxigenin-labeled RNA probes to putative tracheal patterning genes were generated by in vitro transcription. Embryos ranging in age from E9 to E16 were then subjected to whole-mount in situ hybridization using these labeled RNA probes. The RNA probes were then localized using antidigoxigenin antibodies tagged with a reporter molecule. In this manner, the 3-dimensional spatial and temporal expression of putative tracheal patterning genes was examined. Subjects F/VBN mice. RESULTS: In the developing mouse trachea, the expression of Sox9 messenger RNA preceded cartilage ring formation. Sox9 was expressed as 2 distinct longitudinal stripes along the posterolateral aspect of the trachea as early as E9, when the developing trachea is first identified. Collagen 2A1, a cartilage-specific protein, was subsequently expressed in the same longitudinal pattern as Sox9, consistent with the early commitment of Sox9-expressing cells to the cartilage program. As cartilage rings formed, Sox9 and collagen 2A1 was expressed over the lateral and anterior aspects of the trachea. CONCLUSIONS: We have developed a system to study the early expression of genes that may pattern the formation of the trachea. We have identified a gene (Sox9) with a known role in chondrocyte differentiation that is expressed in a highly specific temporal and spatial pattern in the developing upper respiratory tract.

Animals↗

Zygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation.

Maternal expression of the Toll gene is required for the production and the correct spatial organization of all lateral and ventral structures of the Drosophila embryo. We show here that the Toll gene is transcribed zygotically in the embryo and that zygotic expression is important for the viability of the larva. Both genetic and molecular data indicate that the zygotic Toll product has the same biochemical activity as the maternal product. The spatial distribution of the Toll transcript in the embryo was analyzed. In contrast to the uniform distribution of the maternal RNA, the zygotic Toll RNA is present in a complex spatial and temporal pattern in the embryo. A striking feature of this pattern is the correlation of the regions of invaginating cells with sites of accumulation of zygotic Toll RNA.

Animals↗

Targeted localized degradation of Paired protein in Drosophila development.

BACKGROUND: Selective spatial regulation of gene expression lies at the core of pattern formation in the embryo. In the fruit fly Drosophila, localized transcriptional regulation accounts for much of the embryonic pattern. RESULTS: We identified a gene, partner of paired (ppa), whose properties suggest that localized receptors for protein degradation are integrated into regulatory networks of transcription factors to ensure robust spatial regulation of gene expression. We found that the Ppa protein interacts with the Pax transcription factor Paired (Prd) and contains an F-box, a motif found in receptors for ubiquitin-mediated protein degradation. In normal development, Prd functions only in cells in which ppa mRNA expression has been repressed by another segmentation protein, Even-skipped (Eve). When ppa was expressed ectopically in these cells, Prd protein, but not mRNA, levels diminished. When ppa function was removed from cells that express prd mRNA, Prd protein levels increased. CONCLUSIONS: Ppa co-ordinates Prd degradation and is important for expression of Prd to be correctly localized. In the presence of Ppa, Prd protein is targeted for degradation at sites where its mis-expression would disrupt development. In the absence of Ppa, Prd is longer-lived and regulates downstream target genes.

Amino Acid Sequence↗

Pattern formation on trees.

Networks having the geometry and the connectivity of trees are considered as the spatial support of spatiotemporal dynamical processes. A tree is characterized by two parameters: its ramification and its depth. The local dynamics at the nodes of a tree is described by a nonlinear map, giving rise to a coupled map lattice system. The coupling is expressed by a matrix whose eigenvectors constitute a basis on which spatial patterns on trees can be expressed by linear combination. The spectrum of eigenvalues of the coupling matrix exhibit a nonuniform distribution that manifests itself in the bifurcation structure of the spatially synchronized modes. These models may describe reaction-diffusion processes and several other phenomena occurring on heterogeneous media with hierarchical structure.

Journal Article↗

[Physics of biological pattern formation].

In each generation cycle of a higher organism, a complex structure if formed under the instruction of the genes. In this process morphogenetic fields (probably spatial concentration patterns of substances) are involved which elicit cell responses giving rise to visible pattern and form. Autocatalytic short-range activation in conjunction with long-range ("lateral") inhibition is capable of generating striking concentration patterns starting from near-uniform distributions. No features unusual in molecular biology are required, and self-regulatory properties observed experimentally in biological development can be accounted for. Cell responses to morphogenetic fields can include cell differentiation and the generation of bending moments, curvature and form in cell sheets giving rise to defined forms in organs and organisms. It appears that biological pattern formation is explicable on the basis of known physical laws and processes.

Animals↗

Spontaneous pattern formation and genetic invasion in locally mating and competing populations.

We present a theoretical model of evolution of spatially distributed populations in which organisms mate with and compete against each other only locally. We show using both analysis and numerical simulation that the typical dynamics of population density variation is a spontaneous formation of isolated groups due to competition for resources. The resulting spatial separation between groups strongly affects the process of genetic invasion by local reproductive mixing, and spatially inhomogeneous genetic distributions are possible in the final states. We then consider a specific version of this model in the presence of disruptive selection, favoring two fittest types against their genetic intermediates. This case can be simplified to a system that involves just two nonconserved order parameters: population density and type difference. Since the coexistence of two fittest types is unstable in this case, symmetry breaking and coarsening occur in type difference, implying eventual dominance by one type over another for finite populations. However, such coarsening patterns may be pinned by the spontaneously generated spatial separation between isolated groups. The long-term evolution of genetic composition is found to be sensitive to the ratio of the mating and competition ranges, and other parameters. Our model may provide a theoretical basis for consideration of various properties of spatially extended evolutionary processes, including spontaneous formation of subpopulations and lateral invasion of different types.

Journal Article↗

A cluster translocation model may explain the collinearity of Hox gene expressions.

A model is proposed that deals with the observed collinearities (spatial, temporal and quantitative) of Hox gene expression during pattern formation along the primary and secondary axes of vertebrates. In particular, in the proximodistal axis of the developing limb, it is assumed that a morphogen gradient is laid down with its source at the distal tip of the bud. The extracellular signals in every cell of the morphogenetic field are transduced and uniformly amplified so that molecules are produced in the nucleus with appropriate physicochemical properties. These molecules can exert a concentration-dependent force on the Hox cluster. It is assumed that, before activation, the Hox cluster is packaged as an elongated rigid body inside the chromatin and is covered by a coat that prevents the transcription factors reaching the genes of the cluster. The transcription factors are confined to the interchromatin domain and their density decreases with their distance from the chromatin surface. A gradual increase in the extracellular morphogen concentration causes a corresponding increase in the number of the nuclear molecules and the resulting bigger force pushes the Hox cluster toward the interchromatin domain. The step-by-step translocations of the Hox cluster initiate the consecutive exposure of genes to their transcription factors. The model explains how gene activation is triggered and it describes spatial, temporal and quantitative collinearities at the initial stages of gene expression. Some recent experiments of Hox deletions and duplications are accounted for by the model.

Animals↗

Dissipative structures, catastrophes, and pattern formation: a bifurcation analysis.

A model chemical network involving reactions and diffusion is studied. Spatially and temporally ordered solutions of the equations are found by bifurcation theory. These solutions are calculated analytically and their stability is studied. Properties of these dissipative structures are discussed, and a comparison with Thom's theories of morphogenesis is outlined.

Journal Article↗

Activity-regulated cell death contributes to the formation of ON and OFF alpha ganglion cell mosaics.

At maturity, ON and OFF alpha ganglion cells in the cat retina are arrayed in regular mosaics, with adjacent cells commonly forming ON-OFF pairs. In the present study, we investigated the role of activity-mediated ganglion cell death in the formation of such cellular patterns. Because direct measures of ganglion cell mosaics are problematic in the developing retina, we examined the distributions of ON and OFF alpha cells in the postnatal cat retina by assessing the degree to which cells in closest proximity were of opposite sign (i.e., ON-OFF pairs). Computer simulations demonstrated that superimposition of two regular distributions results in a high incidence (approximately 90%) of opposite sign pairs. This is also the case for ON and OFF alpha cells in the mature retina, reflecting the high degree of regularity exhibited by this cell class. In contrast, during the first postnatal month, alpha cells displayed a much lower incidence of opposite sign pairs (approximately 60%), comparable to the superimposition of two simulated random distributions. We also show that there is a 20% loss of alpha cells in the central retina during postnatal development and that this magnitude of loss is sufficient to form regular distributions of ON and OFF cells. To assess the influence of sodium voltage-gated activity on this developmental process, intraocular injections of tetrodotoxin (TTX) were made during the postnatal period of alpha cell loss. When the TTX-treated animals reached maturity, there was a dose-related decrease in the incidence of opposite sign pairs, without any appreciable change in cell density. Moreover, the regularity index of ON and OFF cells was significantly lower than normal in the TTX-treated retinas. These findings demonstrate that a spatially selective pattern of ganglion cell loss contributes to the formation of regular ON and OFF ganglion cell distributions and that such cell loss is regulated by retinal activity.

Animals↗

Receptor-based models with hysteresis for pattern formation in hydra.

In this paper, we propose a new receptor-based model for pattern formation and regulation in a fresh-water polyp, namely hydra. The model is defined in the form of a system of reaction-diffusion equations with zero-flux boundary conditions coupled with a system of ordinary differential equations. The production of diffusible biochemical molecules has a hysteretic dependence on the density of these molecules and is modeled by additional ordinary differential equations. We study the hysteresis-driven mechanism of pattern formation and we demonstrate the advantages and constraints of its ability to explain different aspects of pattern formation and regulation in hydra. The properties of the model demonstrate a range of stationary and oscillatory spatially heterogeneous patterns, arising from multiple spatially homogeneous steady states and switches in the production rates.

Algorithms↗

Experimental study of the dimensionality of black-eye patterns.

The spatial structure of one type of Turing pattern named "black eyes" is studied in experiments using the chlorite-iodide-malonic acid reaction in spatial open reactor. The purpose of the work is to verify (or falsify) two possible theoretical interpretations of black-eye pattern formation: the projection of a body-centered-cubic (bcc) structure onto the plane vertical to the body diagonal and the spatial resonance of larger wave vectors with the fundamental ones. The latter happens when the mode of the larger wave vectors becomes linearly unstable, as the system goes far beyond the onset of Turing bifurcation. Our experimental results give evidence that black-eye patterns are not a projection of the bcc structure, so that the interpretation of a three-dimensional structure can be ruled out. The observations in the experiment also suggest another possible mechanism for the formation of black eyes.

Journal Article↗