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Stripe selection: an intrinsic property of some pattern-forming models with nonlinear dynamics.

In two-dimensional pattern formation, the genesis of stripped rather than spotted patterns may involve preexisting spatial asymmetries, such as unidirectional gradients or asymmetric shape of the pattern-forming domain. In the absence of such asymmetries, some kinds of nonlinear dynamics still lead to striped rather than spotted patterns. We have studied the latter effect both by extensive computer experiments on a range of nonlinear models and by mathematical analysis. We conclude that, when the dynamic equations are written in terms of departure from the unpatterned state, the presence of nonlinearities which are odd functions of these departures (e.g., cubic terms) together with absence of even nonlinearities (e.g., quadratic terms) ensures stripe formation. In computer experiments, we have studied the dynamics of two-morphogen reaction-diffusion models. The mathematical analysis presented in the Appendix shows that the same property exists in more generalized models for pattern formation in the primary visual cortex.

Animals↗

Biochemical pathways of retinoid transport, metabolism, and signal transduction.

Retinoids control the processes of differentiation, proliferation, and apoptosis from the conception of vertebrates through their deaths. It may seem improbable that a few small, simple lipids could contain and communicate such extensive and disparate information as the retinoids, but the permutations possible make this notion plausible. Retinoid actions result from coordinated interplay among more than one hormone and multiple binding proteins, biosynthetic and catabolic enzymes, receptors (acting alone or in combination not only with retinoid but also with other lipophilic hormone receptors), and receptor-response elements. This symphony is conducted in all vertebrates in deliberate spatially and temporally specific patterns. This article reviews the absorption and formation of retinol, the parent and major circulating naturally occurring retinoid; the role of retinol as substrate for biosynthesis of two hormones, i.e., all-trans-retinoic acid (atRA) and 9-cis-retinoic acid (9cRA); the integrated operations of retinoid metabolism and the intracellular retinoid-binding proteins, cellular retinol-binding protein (CRBP), and cellular RA-binding protein (CRABP), which protect (retinoids), serve (as substrate), and control (metabolic reactions); and the mechanism of RA and 9cRA action as activators of the transcription factors RA-receptor (RAR) and the retinoid X receptor (RXR). The discussion offers a mechanistic rationale for the pleiotropic actions of retinoids.

Animals↗

Immunohistological and ultrastructural study of the developing tendons of the avian foot.

The aim of the present report is to provide a detailed description of the morphogenesis and initial differentiation of the long tendons of the chick foot, the long autopodial tendons (LAT), from day 6 to day 11 of development. The fine structure of the developing LAT was studied by light and transmission electron microscopy. The characterization by immunofluorescent techniques of the extracellular matrix was performed using laser scanning confocal (tenascin, elastin, fibrillin, emilin, collagen type I, II, III, IV and VI) or routine fluorescence (tenascin, 13F4) microscopy. In addition, cell proliferation in pretendinous blastemas was analyzed by the detection of BrdU incorporation by immunofluorescence. The light microscopic analysis permitted the identification of different stages during LAT morphogenesis. The first stage is the formation of a thick ectoderm-mesenchyme interface along the digital rays, followed by the differentiation of the "mesenchyme lamina", an extracellular matrix tendon precursor, and ending with the formation and differentiation of the cellular condensation that forms the tendon blastema around this lamina. The immunofluorescence study revealed the presence and arrangement of the different molecules analyzed. Tenascin and collagen type VI are precocious markers of the developing tendons and remain present during the whole process of tendon formation. Collagen type I becomes mainly restricted to the developing tendons from day 7.5. Collagens type II and IV are never detected in the developing tendons, while a faint labeling for collagen type III is first detected at day 7. The analysis of the distribution of the elastic matrix components in the developing tendons is a major contribution of our study. Elastin was detected in the periphery of the tendons from day 8 and also in fibrils anchoring the tendons to the skeletal elements. At the same stage, emilin strongly stains the core of the tendon rods, while fibrillin is detected a little later. Our study indicates the existence of an ectoderm-mesoderm interaction at the first stage of the tendon formation. In addition, our results show the different spatial and temporal pattern of distribution of extracellular matrix molecules in developing tendons. Of special importance are the findings concerning the tendinous elastic matrix and its possible role in tendon maturation and stabilization.

Animals↗

Lesions of excitatory pathways reduce hippocampal cell death after transient forebrain ischemia in the gerbil.

Transient forebrain ischemia produces a spatially and temporally selective pattern of neuronal degeneration in the hippocampal formation of the Mongolian gerbil. Ischemic neuronal death has been suggested to depend on the activation of excitatory hippocampal pathways that project to the vulnerable neurons. This idea was tested by examining the effect of a unilateral entorhinal cortical lesion or a unilateral knife cut lesion of intrahippocampal pathways on the neuropathology produced by 5 min of complete forebrain ischemia. A prior lesion of either the ipsilateral entorhinal cortex or the mossy fiber and Schaffer collateral-commissural pathways partially prevented the destruction of CA1b pyramidal cells in most animals. It did not, however, reduce the extent of ischemic neuronal death in any other hippocampal subfield. Within area CA1b, an entorhinal lesion protected an average of 23% of the pyramidal cells and a transection of both mossy and Schaffer collateral-commissural fibers protected an average of 36.5%. CA1b pyramidal cells saved from ischemia-induced degeneration appeared clearly abnormal when stained with cresyl violet or by silver impregnation. It is suggested that lesions of excitatory pathways attenuate ischemic damage to area CA1b by directly or indirectly reducing the level of synaptic excitation onto the vulnerable neurons. However, only a relatively small percentage of hippocampal neurons can be protected by these lesions in the gerbil ischemia model and there is reason to believe that the neurons protected in this manner may not be electrophysiologically competent. Synaptic excitation therefore appears to play an important, but not an essential, role in this model of ischemic brain damage.

Afferent Pathways↗

XY chromosome behaviour in the germ-line of the human male: a FISH analysis of spatial orientation, chromatin condensation and pairing.

We have used multicolour fluorescence in situ hybridization to study the behaviour of the X and Y chromosomes in relation to a representative autosome, chromosome 1, on air-dried testicular preparations from normal fertile human males. In a proportion of Sertoli cells at interphase as well as spermatogonial metaphases there is an apparent selective undercondensation of the heterochromatic block of the long arm of the Y, which may be of functional significance with respect to Y-specific gene activity, initiating and maintaining spermatogenesis; we suggest that this may involve a mechanism similar to heterochromatin position-effect variegation in Drosophila. In the supporting Sertoli as well as pre-meiotic and leptotene cells the X and Y occupy relatively restricted domains at opposite poles of the nuclear membrane, while the chromosome 1 centromere regions are located interstitially and appear prealigned. The XY pairing and 'sex vesicle' formation comprises a complex series of spatial movement and differential condensation patterns. On the basis of these observations we propose that: the XIST/Xist gene, known to be involved in somatic X inactivation, imposes a chromatin reorganization leading to bending at the X-inactivation centre both at first meiotic prophase in males and in the soma in females; and the differential X and Y segments are protected from potentially deleterious meiotic exchanges by their separate spatial orientation. In addition, there is an indication that the timing of pairing and first meiotic segregation of the sex chromosomes is different, and precocious in comparison to the pairing and segregation of the autosomes, which may explain the high incidence of sex chromosome aneuploidy in sperm.

Animals↗

Spatial quantification of Mn2+ and Mn3+ concentrations in the Mn-catalyzed 1,4-cyclohexanedione/acid/bromate reaction using magnetic resonance imaging.

This paper presents a magnetic resonance imaging (MRI) method for quantifying the spatial concentrations of the paramagnetic species Mn2+ and Mn3+, during pattern formation, in the manganese-catalyzed 1,4-cyclohexanedione-acid-bromate reaction. The relaxivity of each species was measured, which enabled their concentration to be calculated from nuclear magnetic resonance T2 relaxation times. Images were acquired using the fast spin-echo imaging method RARE. By determining the relation, in these experiments, between signal intensity and T2 relaxation time, it was possible to produce T2 maps from the images. These T2 maps were then used to produce concentration maps for the oxidized (Mn3+) and reduced (Mn2+) states of the catalyst.

Letter↗

Drosophila DEG/ENaC pickpocket genes are expressed in the tracheal system, where they may be involved in liquid clearance.

The Drosophila tracheal system and mammalian airways are branching networks of tubular epithelia that deliver oxygen to the organism. In mammals, the epithelial Na(+) channel (ENaC) helps clear liquid from airways at the time of birth and removes liquid from the airspaces in adults. We tested the hypothesis that related Drosophila degenerin (DEG)/ENaC family members might play a similar role in the fly. Among 16 Drosophila DEG/ENaC genes, called pickpocket (PPK) genes, we found 9 expressed in the tracheal system. By in situ hybridization, expression appeared in late-stage embryos after tracheal tube formation, with individual PPK genes showing distinct temporal and spatial expression patterns as development progressed. Promoters for several PPK genes drove reporter gene expression in the larval and adult tracheal systems. Adding the DEG/ENaC channel blocker amiloride to the medium inhibited liquid clearance from the trachea of first instar larvae. Moreover, when RNA interference was used to silence PPK4 and PPK11, larvae failed to clear tracheal liquid. These data suggest substantial molecular diversity of DEG/ENaC channel expression in the Drosophila tracheal system where the PPK proteins likely play a role in Na(+) absorption. Extensive similarities between Drosophila and mammalian airways offer opportunities for genetic studies that may decipher further the structure and function of DEG/ENaC proteins and development of the airways.

Amiloride↗

Models of spatial and orientational self-organization of microtubules under the influence of gravitational fields.

Tabony and co-workers [C. Papaseit, N. Pochon, and J. Tabony, Proc. Natl. Acad. Sci. U.S.A. 97, 8364 (2000)] showed that the self-organization of microtubules from purified tubulin solutions is sensitive to gravitational conditions. In this paper, we propose two models of spatial and orientational self-organization of microtubules in a gravitational field. First, the spatial model is based on the dominant chemical kinetics. The pattern formation of microtubule concentration is obtained (1) in terms of a moving kink in the limit when the disassembly rate is negligible, and (2) for the case of no free tubulin and only assembled microtubules present. Second, the orientational pattern of striped microtubule domains is consistent with predictions from a phenomenological Landau-Ginzburg free energy expansion in terms of an orientational order parameter.

Animals↗

The novel cytosolic RING finger protein dactylidin is up-regulated in brains of patients with Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a progressive degeneration of neurons along with deposition of amyloid plaques and the formation of neurofibrillary tangles. Neurodegeneration in AD follows both a spatial pattern of selective vulnerability and temporal staging of affected neurons. In order to address transcriptional changes associated with this selective vulnerability, we used subtractive hybridization of transcripts derived from human frontal cortex, which degenerates in late stages of AD, against transcripts of the inferior temporal cortex, which is affected both heavily and early in the course of AD. Moreover, we compared these to brain sections obtained from age-matched control subjects. We isolated a differentially expressed novel gene encoding a polypeptide that contained an amino-terminal C3HC4 RING finger domain, called dactylidin. It is ubiquitously expressed in all tissues examined and in situ hybridization of mouse brain sections revealed specific expression in neurons. Further, heterologous expression studies revealed a cytoplasmic localization of dactylidin and as all known cytoplasmic RING finger proteins function as ubiquitin protein ligases, an E3-like ligase function of dactylidin is probable. However, the up-regulation of dactylidin in highly vulnerable brain tissues of AD patients was confirmed by a quantitative PCR approach, suggesting that dactylidin may function early in the progression of neurodegenerative diseases.

Aged↗

Impaired cued and contextual memory in NPAS2-deficient mice.

Neuronal PAS domain protein 2 (NPAS2) is a basic helix-loop-helix (bHLH) PAS domain transcription factor expressed in multiple regions of the vertebrate brain. Targeted insertion of a beta-galactosidase reporter gene (lacZ) resulted in the production of an NPAS2-lacZ fusion protein and an altered form of NPAS2 lacking the bHLH domain. The neuroanatomical expression pattern of NPAS2-lacZ was temporally and spatially coincident with formation of the mature frontal association/limbic forebrain pathway. NPAS2-deficient mice were subjected to a series of behavioral tests and were found to exhibit deficits in the long-term memory arm of the cued and contextual fear task. Thus, NPAS2 may serve a dedicated regulatory role in the acquisition of specific types of memory.

Animals↗

Identification of a retinoic acid response element upstream of the murine Hox-4.2 gene.

Hox genes play an important role in the process of vertebrate pattern formation, and their expression is intricately regulated both temporally and spatially. All-trans-retinoic acid (RA), a physiologically active metabolite of vitamin A, affects the expression of a large number of Hox genes in vitro and in vivo. However, the regulatory mechanisms underlying the RA response of these genes have not been extensively studied, and no response element for RA receptors (RARs) has been characterized in a Hox regulatory region. The expression of murine Hox-4.2 and its human homolog, HOX4B, is increased in embryonal carcinoma (EC) cell lines upon RA treatment (M. S. Featherstone, A. Baron, S. J. Gaunt, M.-G. Mattei, and D. Duboule, Proc. Natl. Acad. Sci. USA 85:4760-4764, 1988; A. Simeone, D. Acampora, V. Nigro, A. Faiella, M. D'Esposito, A. Stornaiuolo, F. Mavilio, and E. Boncinelli, Mech. Dev. 33:215-228, 1991). Using transient expression assays, we showed that luciferase reporter gene constructs carrying genomic sequences located upstream of Hox-4.2 responded to RA in murine P19 EC cells. A 402-bp NcoI fragment was necessary for the RA responsiveness of reporter constructs. This fragment contained a regulatory element, 5'-AGGTGA(N)5AGGTCA-3', that closely resembles the consensus sequence for an RA response element. The Hox-4.2 RA response element was critical for the RA induction and specifically bound RARs. In addition, the response to RA could be inhibited by expressing a dominant negative form of RAR alpha in transfected P19 EC cells. These results suggested that Hox-4.2 is a target for RAR-mediated regulation by RA.

Animals↗

Potential morphogens involved in pattern formation during Dictyostelium differentiation.

Upon starvation, Dictyostelium amoebae aggregate together and then differentiate into either the stalk or spore cells that, respectively, form the stalk and sorus of the fruiting body. During differentiation, the prestalk and prespore cells become spatially segregated in a clearly defined developmental pattern. Several low molecular weight molecules that influence cell type determination during in vitro differentiation have been identified. The possible role of these molecules as morphogens, responsible for the formation of the developmental pattern, is discussed.

Adenosine↗

Formation of multifractal population patterns from reproductive growth and local resettlement.

We consider the general character of the spatial distribution of a population that grows through reproduction and subsequent local resettlement of new population members. We present several simple one- and two-dimensional point placement models to illustrate possible generic behavior of these distributions. We show, numerically and analytically, that these models all lead to multifractal spatial distributions of population. Additionally, we make qualitative links between our models and the example of the Earth at Night image, showing the Earth's nighttime man-made light as seen from space. The Earth at Night data suffer from saturation of the sensing photodetectors at high brightness ("clipping"), and we account for how this influences the determined dimension spectrum of the light intensity distribution.

Animals↗

Pattern formation as a signature of quantum degeneracy in a cold exciton system.

The development of a Turing instability to a spatially modulated state in a photoexcited electron-hole system is proposed as a novel signature of exciton Bose statistics. We show that such an instability, driven by kinetics of exciton formation, can result from stimulated processes that build up near quantum degeneracy. The stability of an electron-hole interface which describes recently observed exciton rings is analyzed. Interface instability occurs below a critical temperature, with a periodic 1D pattern developing via a continuous (type II) transition, in a qualitative agreement with observations.

Journal Article↗

Pathological pattern formation and cortical propagation of epileptic seizures.

The stochastic partial differential equations (SPDEs) stated by Steyn-Ross and co-workers constitute a model of mesoscopic electrical activity of the human cortex. A simplification in which spatial variation and stochastic input are neglected yields ordinary differential equations (ODEs), which are amenable to analysis by techniques of dynamical systems theory. Bifurcation diagrams are developed for the ODEs with increased subcortical excitation, showing that the model predicts oscillatory electrical activity in a large range of parameters. The full SPDEs with increased subcortical excitation produce travelling waves of electrical activity. These model results are compared with electrocortical data recorded at two subdural electrodes from a human subject undergoing a seizure. The model and observational results agree in two important respects during seizure: (i) the average frequency of maximum power, and (ii) the speed of spatial propagation of voltage peaks. This suggests that seizing activity on the human cortex may be understood as an example of pathological pattern formation. Included is a discussion of the applications and limitations of these results.

Cerebral Cortex↗

Expression of doublecortin correlates with neuronal migration and pattern formation in diverse regions of the developing chick brain.

The development of functional layers in the brain involves spatially and temporally regulated gene expression. Through cDNA library screening, we have identified genes that are expressed in a neural-specific manner during brain development. Sequencing and expression data indicate that one of the clones, 18C15, is the chick homologue of doublecortin, a human X-linked gene found to be mutated in subcortical laminar heterotopia (double cortex syndrome) and lissencephaly. The 18C15 mRNA contains multiple motifs that are known to regulate mRNA stability in response to inductive signals, and these motifs are conserved between the chick and human sequences. Doublecortin is found to be expressed at peak levels during early development of the cerebellum and forebrain, and is expressed in other regions including the tectum, spinal cord, and dorsal root ganglia. This study demonstrates both spatial and temporal regulation of doublecortin expression in the chick, which is associated with early events in brain development, including neuronal migration.

3' Untranslated Regions↗

Temporal and spatial effects of Sonic hedgehog signaling in chick eye morphogenesis.

Proper dorsal--ventral pattern formation of the optic cup is essential for vertebrate eye morphogenesis and retinotectal topographic mapping. Previous studies have suggested that midline tissue-derived Sonic hedgehog (Shh) molecules play critical roles in establishing the bilateral eye fields and in determining the proximal--distal axis of the eye primordium. Here, we have examined the temporal requirements for Shh during the optic vesicle to optic cup transition and after early optic cup formation in chick embryos. Both misexpressing Shh by virus and blocking Shh activity by antibodies resulted in disruption of ventral ocular tissues. Decreasing endogenous Shh signals unexpectedly revealed a sharp morphological boundary subdividing dorsal and ventral portions of the optic cup. In addition, Shh signals differentially influenced expression patterns of genes involved in ocular tissue specification (Pax6, Pax2, and Otx2) and dorsal--ventral patterning (cVax) within the ventral but not dorsal optic cup. Ectopic Shh suppressed expression of Bone Morphogenetic Protein 4 (BMP4) in the dorsal retina, whereas reducing endogenous Sonic hedgehog activity resulted in a ventral expansion of BMP4 territory. These results demonstrate that temporal requirements for Shh signals persist after the formation of the optic cup and suggest that the early vertebrate optic primordium may be subdivided into dorsal and ventral compartments. We propose a model in which ventrally derived Shh signals and dorsally restricted BMP4 signals act antagonistically to regulate the growth and specification of the optic primordium.

Animals↗

Altered TCR signaling from geometrically repatterned immunological synapses.

The immunological synapse is a specialized cell-cell junction that is defined by large-scale spatial patterns of receptors and signaling molecules yet remains largely enigmatic in terms of formation and function. We used supported bilayer membranes and nanometer-scale structures fabricated onto the underlying substrate to impose geometric constraints on immunological synapse formation. Analysis of the resulting alternatively patterned synapses revealed a causal relation between the radial position of T cell receptors (TCRs) and signaling activity, with prolonged signaling from TCR microclusters that had been mechanically trapped in the peripheral regions of the synapse. These results are consistent with a model of the synapse in which spatial translocation of TCRs represents a direct mechanism of signal regulation.

Amino Acid Motifs↗