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StuA is required for cell pattern formation in Aspergillus.

The stunted (stuA) gene product is required for the orderly differentiation and spatial organization of cell types of the Aspergillus nidulans conidiophore. Expression of the stuA gene is complex. Two transcripts, stuA alpha and stuA beta, are initiated from separate promoters. Transcription of both RNAs increases approximately 50-fold during the establishment of developmental competence. Induction-dependent transcriptional and post-transcriptional regulatory mechanisms further enhance expression 15-fold. Consistent with the latter observation, both transcripts have structural features characteristic of RNAs subject to translational control. Conidiophore morphogenesis requires regulatory interactions between the products of the stuA, bristle (brlA), and abacus (abaA) genes. Enhanced stunted expression is cell type specific and dependent on a functional BrlA protein. StuA affects the spatial localization of AbaA by acting directly, or indirectly, to repress abaA expression.

Amino Acid Sequence↗

Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing.

In the early Drosophila embryo, BMP-type ligands act as morphogens to suppress neural induction and to specify the formation of dorsal ectoderm and amnioserosa. Likewise, during pupal wing development, BMPs help to specify vein versus intervein cell fate. Here, we review recent data suggesting that these two processes use a related set of extracellular factors, positive feedback, and BMP heterodimer formation to achieve peak levels of signaling in spatially restricted patterns. Because these signaling pathway components are all conserved, these observations should shed light on how BMP signaling is modulated in vertebrate development.

Animals↗

Interactions and fates of avian craniofacial mesenchyme.

Craniofacial mesenchyme is composed of three mesodermal populations - prechordal plate, lateral mesoderm and paraxial mesoderm, which includes the segmented occipital somites and the incompletely segmented somitomeres - and the neural crest. This paper outlines the fates of each of these, as determined using quail-chick chimaeras, and presents similarities and differences between these cephalic populations and their counterparts in the trunk. Prechordal and paraxial mesodermal populations are the sources of all voluntary muscles of the head. The latter also provides most of the connective precursors of the calvaria, occipital, otic-parietal and basisphenoid tissues. Lateral mesoderm is the source of peripharyngeal connective tissues; the most rostral skeletal tissues it forms are the laryngeal and tracheal cartilages. When migrating neural crest cells encounter segmented paraxial mesoderm (occipital and trunk somites), most move into the region between the dermamyotome and sclerotome in the cranial half of each somite. In contrast, most cephalic crest cells migrate superficial to somitomeres. There is, however, a small subpopulation of the head crest that invades somitomeric mesoderm. These cells subsequently segregate presumptive myogenic precursors of visceral arch voluntary muscles from underlying mesenchyme. In the neurula-stage avian embryo, all paraxial and lateral mesodermal populations contain precursors of vascular endothelial cells, which can be detected in chimaeric embryos using anti-quail endothelial anti-bodies. Some of these angioblasts differentiate in situ, contributing directly to pre-existing vessels or forming isolated, nonpatent, cords that subsequently vesiculate and fuse with nearby vessels. Many angioblasts migrate in all directions, invading embryonic mesenchymal and epithelial tissues and participating in new blood vessel formation in distant sites. The interactions leading to proper spatial patterning of craniofacial skeletal, muscular, vascular and peripheral neural tissues has been studied by performing heterotopic transplants of each of these mesodermal and neural crest populations. The results consistently indicate that connective tissue precursors, regardless of their origin, contain spatial information used by the precursors of muscles and blood vessels and by outgrowing peripheral nerves. Some of these connective tissue precursors (e.g. the neural crest, paraxial mesoderm) acquire their spatial programming while in association with the central nervous system or developing sensory epithelia (e.g. otic, optic, nasal epithelia).

Animals↗

Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy.

Neurofibrillary tangles form in a specific spatial and temporal pattern in Alzheimer's disease. Although tangle formation correlates with dementia and neuronal loss, it remains unknown whether neurofibrillary pathology causes cell death. Recently, a mouse model of tauopathy was developed that reversibly expresses human tau with the dementia-associated P301L mutation. This model (rTg4510) exhibits progressive behavioral deficits that are ameliorated with transgene suppression. Using quantitative analysis of PHF1 immunostaining and neuronal counts, we estimated neuron number and accumulation of neurofibrillary pathology in five brain regions. Accumulation of PHF1-positive tau in neurons appeared between 2.5 and 7 months of age in a region-specific manner and increased with age. Neuron loss was dramatic and region-specific in these mice, reaching over 80% loss in hippocampal area CA1 and dentate gyrus by 8.5 months. We observed regional dissociation of neuronal loss and accumulation of neurofibrillary pathology, because there was loss of neurons before neurofibrillary lesions appeared in the dentate gyrus and, conversely, neurofibrillary pathology appeared without major cell loss in the striatum. Finally, suppressing the transgene prevented further neuronal loss without removing or preventing additional accumulation of neurofibrillary pathology. Together, these results imply that neurofibrillary tangles do not necessarily lead to neuronal death.

Aging↗

[Photomorphogenesis].

The normal development of the higher plant occurs only in light (photomorphogenesis). The effect of light is due to intracellular development of a morphogenetically active effector molecule (Pfr, a chromoprotein). The point in question is, by which pathways the homeostasis of development (the course of development directed by endogenic factors) and the environmental factor "light" may act together in photomorphogenesis in order to accomplish the normal development of plants. Physiological and molecular analysis of photomorphogenesis is to contribute basically to the problem of surveying the pathways of gens and environmental influences in determining the characteristics of higher organisms, man included. The logical order of the phenomena is shown to have the precedence of an attempt for molecular analysis of photomorphogenesis. A result of the logical order is the insight that all the phenomena induced by Pfr present the spatial and temporal pattern of "primary differentiation". This primary differentiation (= formation of the specific competence) does not depend on light (developmental homeostasis). The photomorphogenesis (= development through the presence of Pfr of the pattern due to the primary differentiation), in accordance with the present knowledge is to be attributed to differential enzymatic induction and repression. This opinion is confirmed by examples. The correlation between the enzymatic activity and the structure (form, shape) still remains an unsolved problem.

Ascorbate Oxidase↗

Growth factor expression during rat development: a comparison of TGF-beta 3, TGF-alpha, bFGF, PDGF and PDGF-R.

At least part of the mechanism underlying fetal development appears to be the production of a number of growth factors considered important in the process of tumour formation. Using immunocytochemistry, we have investigated the temporal and spatial pattern of expression of some of the important growth factors, by the fetus. We describe here the cellular localization of transforming growth factor beta 3 (TGF-beta 3), platelet derived growth factor (PDGF) and its receptor (PDGF-R), TGF-alpha and basic fibroblast growth factor (bFGF) in the fetal rat from day 13 to 21 of gestation. Using antisera raised against an N-terminal portion of TGF-beta 3, immunoreactivity peaked around day 16 and was seen predominantly within epithelial cells. However, using antisera raised against the C-terminal of this molecule immunoreactivity was seen exclusively within the extracellular matrix underlying adjacent epithelia, and was maintained up until day 21 of gestation. Strong expression of TGF-alpha was seen in cells of most organs throughout the gestation period studied. Immunoreactivity for bFGF, PDGF and PDGF-R peaked around day 18 in both epithelial and mesenchymal cells of all major organ systems and then declined by day 21. These data suggest distinct roles for each factor during embryogenesis and tumorigenesis.

Animals↗

The BMP proteins in bone formation and repair.

From recent advances in the fields of bone biology and pattern formation, the first clues to our understanding of embryonic skeletal development are beginning to emerge. This complex process involves an integration of spatial patterning and the differentiation of specialized cells that make up bone and cartilage. The result is a scale model of the mature skeleton which is able to grow in size to fit the adult body plan. In the mature animal, bone repair after injury appears to be similar to bone formation in the embryo, suggesting that analogous mechanisms for the control of bone formation may exist in the adult and embryonic skeletons.

Animals↗

Peripherin- and CGRP-immunoreactive nerve fibers in rat molars have different locations and developmental timing.

UNLABELLED: Developing rat molars gain mature sensitivity to electric stimulation at 4-5 weeks after eruption, but the related mechanisms are incompletely understood. Preliminary studies showed weak co-localization of calcitonin gene-related peptide (CGRP) immunoreactivity (IR) with peripherin (PER) or neurofilament protein (NF) in rat molar nerve fibers, while the latter two co-localized extensively. OBJECTIVE: Our goal was to compare timing and location of PER-IR and CGRP-IR innervation in rat first molars during tooth maturation. METHODS: We used single and double immunocytochemistry to study molars of rats aged 10 days to 1 year. Neural patterns were compared with odontoblast maturation stages, dentinogenesis, formation of cell-free and cell-rich zones, and root closure. RESULTS: Spatial and temporal patterns showed that most CGRP-IR and PER-IR have different terminal domains in teeth. PER-IR fibers were well established among immature odontoblasts prior to tooth eruption, but CGRP-IR fibers were absent. Two weeks after eruption of first molars, many CGRP-IR beaded fibers entered dentin, the larger PER-IR fibers began shifting away from odontoblasts towards the pulp, and the symmetrical PER-IR pulpal pattern was being established. The CGRP-IR fibers continued to increase their asymmetric dentinal innervation until root growth was completed, during which time odontoblasts matured, the cell-free and cell-rich zones appeared, and roots closed. CONCLUSIONS: Sensory maturation of rat molars coincides with closed root apices, extensive innervation of dentin by CGRP-IR nerve fibers, and the appearance of the mature avascular odontoblast layer next to cell-free and cell-rich zones in the pulp horns.

Animals↗

Contribution of hippocampal place cell activity to learning and formation of goal-directed navigation in rats.

Although extensive behavioral studies have demonstrated that hippocampal lesions impair navigation toward specific places, the role of hippocampal neuronal activity in the development of efficient navigation during place learning remains unknown. The aim of the present study was to investigate how hippocampal neuronal activity changes as rats learn to navigate efficiently to acquire rewards in an open field. Rats were pre-trained in a random reward task where intracranial self-stimulation rewards were provided at random locations. Then, the rats were trained in a novel place task where they were rewarded at two specific locations as they repeatedly shuttled between them. Hippocampal neuronal activity was recorded during the course of learning of the place task. The rats learned reward sites within several sessions, and gradually developed efficient navigation strategies throughout the learning sessions. Some hippocampal neurons gradually changed spatial firing as the learning proceeded, and discharged robustly near the reward sites when efficient navigation was established. Over the learning sessions, the neuronal activity was highly correlated to formation of efficient shuttling trajectories between the reward sites. At the end of the experiment, spatial firing patterns of the hippocampal neurons were re-examined in the random reward task. The specific spatial firing patterns of the neurons were preserved if the rats navigated, as if they expected to find rewards at the previously valid locations. However, those specific spatial firing patterns were not observed in rats pursuing random trajectories. These results suggest that hippocampal neurons have a crucial role in formation of an efficient navigation.

Action Potentials↗

Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus.

Axial pattern formation is sustained in the mammalian gut epithelium despite rapid and continuous renewal of its four principal cell lineages. The mouse and rat liver fatty acid-binding protein (L-FABP) genes (Fabpl) represent an excellent model for understanding the mechanisms that determine differentiation-dependent, cell lineage-specific, and distinct regional patterns of expression along the crypt-to-villus and duodenal-to-ileal axes of the gut, as well as within the liver acinus. We have used transgenic mice to map cis-acting elements in rat Fabpl that control these patterns of gene expression. Seven transgenes were analyzed, representing sequential deletions of the 5'-nontranscribed domain of Fabpl linked to the human growth hormone (hGH) gene beginning at its nucleotide +3 (L-FABP/hGH+3). Several pedigrees of mice containing each one of the L-FABP/hGH+3 transgenes were examined at the end of their 8th and 20th weeks of postnatal life using immunocytochemical and RNA hybridization analyses. A remarkably compact sequence spanning nucleotides -132 to +21 of Fabpl is sufficient to establish and maintain a distribution of reporter mRNA and protein in villus-associated enterocytes located along the duodenal-to-ileal axis of the gut that resembles the pattern of expression of the endogenous Fabpl gene. L-FABP-132 to +21/hGH+3 is also expressed in surface and pit mucous cells of gastric units and in enterocytes located in the colonic homologs of small intestinal villi, the surface epithelial cuffs. This pattern of transgene expression in the stomach and colon recapitulates that of the intact endogenous donor rat Fabpl but not that of mouse Fabpl, which is silent in these proximal and distal segments of the gastrointestinal tract. Analysis of mice containing L-FABP-4000 to +21/hGH+3, L-FABP-1600 to +21/hGH+3, L-FABP-596 to +21/hGH+3, L-FABP-246 to +21/hGH+3, and L-FABP-186 to +21/hGH+3 indicate that Fabpl's cephalocaudal gradient is influenced by cis-acting suppressors of cecal and colonic expression located between nucleotides -4000 and -1600 and by cis-acting activators of cecal and colonic expression located between nucleotides -597 and -351. L-FABP-132 to +21/hGH+3 is precociously activated in proliferating and nonproliferating epithelial cells located in intestinal crypts. The suppressor(s) of L-FABP accumulation in crypt epithelial cell populations are not represented between nucleotides -4000 and +21, indicating that different cis-acting sequences regulate regional and differentiation-dependent patterns of Fabpl expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

Mechanisms of dorsal-ventral axis determination in Drosophila embryos revealed by cytoplasmic transplantations.

The establishment of the dorsal-ventral pattern in Drosophila embryos depends on a signal transduction process: a putative extracellular ligand released into the perivitelline space surrounding the embryo binds to the Toll receptor. Toll activation triggers the formation of the nuclear gradient of dorsal protein, the morphogen of the dorsal-ventral axis. Here, I analyse the dorsal protein distribution and the expression of zygotic dorsal-ventral genes in Toll- embryos that have been injected with wild-type cytoplasm under a variety of different injection conditions. Injections into two positions within a single embryo lead to the formation of two dorsal-ventral patterns in one embryo, allowing the analysis of interactions between pattern-forming processes. The results of single and double injections suggest that the spatial information for the embryonic dorsal-ventral axis is largely derived from spatial cues present in the extraembryonic compartment, which restrict the release of the putative Toll ligand. They argue against a Toll-dependent pattern-formation process employing local self-enhancement and lateral inhibition to enhance a weak initial asymmetry. The putative Toll ligand appears to originate from a ventrally restricted zone which extends along the entire anterior-posterior axis. Ligand diffusion or its graded release are required to determine the slope of the nuclear dorsal protein gradient. Both the Toll receptor and the putative ligand of Toll are in excess in wild-type embryos. Since spatial information for the embryonic dorsal-ventral axis is already present in the vitelline membrane or the perivitelline space, it is most likely generated during oogenesis. Oogenic pattern formation is also responsible for the perpendicular orientation the dorsal-ventral axis maintains with respect to the anterior-posterior axis.

Animals↗

Plasma membrane H+-ATPase is involved in auxin-mediated cell elongation during wheat embryo development.

Previous investigations suggested that specific auxin spatial distribution due to auxin movements to particular embryonic regions was important for normal embryonic pattern formation. To gain information on the molecular mechanism(s) by which auxin acts to direct pattern formation in specific embryonic regions, the role of a plasma membrane (PM) ATPase was evaluated as downstream target of auxin in the present study. Western-blot analysis revealed that the PM H(+)-ATPase expression level was significantly increased by auxin in wheat (Triticum aestivum) embryos (two-three times increase). In bilaterally symmetrical embryos, the spatial expression pattern of the PM H(+)-ATPase correlates with the distribution pattern of the auxin analog, tritiated 5-azidoindole-3-acetic acid. A strong immunosignal was observed in the abaxial epidermis of the scutellum and in the epidermal cells at the distal tip of this organ. Pseudoratiometric analysis using a fluorescent pH indicator showed that the pH in the apoplast of the cells expressing the PM H(+)-ATPase was in average more acidic than the apoplastic pH of nonexpressing cells. Cellulose staining of living embryos revealed that cells of the scutellum abaxial epidermis expressing the ATPase were longer than the scutellum adaxial epidermal cells, where the protein was not expressed. Our data indicate that auxin activates the proton pump resulting in apoplastic acidification, a process contributing to cell wall loosening and elongation of the scutellum. Therefore, we suggest that the PM H(+)-ATPase is a component of the auxin-signaling cascade that may direct pattern formation in embryos.

Cell Division↗

Spatiotemporal dynamics near a supercritical Turing-Hopf bifurcation in a two-dimensional reaction-diffusion system.

Pattern formation in semiconductor heterostructures is studied on the basis of a spatially two-dimensional model of reaction-diffusion type. In particular, we investigate the neighborhood of a codimension-two Turing-Hopf instability by analytical methods. Amplitude equations are derived which predict the absence of mixed modes but extended ranges of bistability between homogeneous oscillatory states and hexagonal Turing patterns. Our results are confirmed by numerical simulations. The features are not confined to a neighborhood of the bifurcation point so that the conclusions of the weakly nonlinear analysis explain the observations in large portions of the parameter space at least qualitatively

Journal Article↗

Spatial distribution of cardiac transmembrane potentials around an extracellular electrode: dependence on fiber orientation.

Recent theoretical models of cardiac electrical stimulation or defibrillation predict a complex spatial pattern of transmembrane potential (Vm) around a stimulating electrode, resulting from the formation of virtual electrodes of reversed polarity. The pattern of membrane polarization has been attributed to the anisotropic structure of the tissue. To verify such model predictions experimentally, an optical technique using a fluorescent voltage-sensitive dye was used to map the spatial distribution of Vm around a 150-microns-radius extracellular unipolar electrode. An S1-S2 stimulation protocol was used, and vm was measured during an S2 pulse having an intensity equal to 10x the cathodal diastolic threshold of excitation. The recordings were obtained on the endocardial surface of bullfrog atrium in directions parallel and perpendicular to the cardiac fibers. In the longitudinal fiber direction, the membrane depolarized for cathodal pulses (and hyperpolarized for anodal pulses) but only in a region within 445 +/- 112 microns (and 616 +/- 78 microns for anodal pulses) from the center of the electrode (n = 9). Outside this region, vm reversed polarity and reached a local maximum at 922 +/- 136 microns (and 988 +/- 117 microns for anodal pulses) (n = 9). Beyond this point vm decayed to zero over a distance of 1.5-2 mm. In the transverse fiber direction, the membrane depolarized for cathodal pulses (and hyperpolarized for anodal pulses) at all distances from the electrode. The amplitude of the response decreased with distance from the electrode with an exponential decay constant of 343 +/- 110 microns for cathodal pulses and 253 +/- 91 microns for anodal pulses (n = 7). The results were qualitatively similar in both fiber directions when the atrium was bathed in a solution containing ionic channel blockers. A two-dimensional computer model was formulated for the case of highly anisotropic cardiac tissue and qualitatively accounts for nearly all the observed spatial and temporal behavior of vm in the two fiber directions. The relationships between vm and both the "activating function" and extracellular potential gradient are discussed.

Animals↗

A clock and trail model for somite formation, specialization and polarization.

We present some theoretical considerations about the initial process of pre-patterning during embryonic segmentation, with particular reference to somite formation. We first suggest that the pre-pattern is a stable spatial sinusoidal (or, at least, periodic) wave. The periodic wave originates from an oscillator ("clock") in the proliferative region that gives rise to the cells. At the moment the cells leave the proliferative or "progress" zone, or somewhat later, a permanent record is made of the current state of the oscillation, which cells then keep during their pre-somitic phase, before explicit somite and somite boundary formation. Thus, a trail is left behind the progress zone in the form of a spatial sine wave. Second, we also observe that the factors involved in the progress-zone clock and its wave-like trail may form multimers, which will oscillate with higher space-time frequency and thus shorter wavelengths than the monomers. Whether or not our first suggestion is correct, this phenomenon may account for multiple wavelengths in somitogenesis, and may thus encompass somite formation, but also somite polarization (half-wavelength) into anterior and posterior halves, as well as the puzzling observation that expression of her1 in zebrafish is in primordia of alternating somites, i.e. it exhibits a 2-somite wavelength.

Animals↗

Mechanical modulation of tenascin-C and collagen-XII expression during avian synovial joint formation.

The objective of this study was to investigate how temporal and spatial patterns of characteristic extracellular matrix molecules are altered in the absence of normal functional skeletal muscle contractions during avian synovial joint development. By using in situ detection of protein and mRNA expression in developing avian feet and femorotibial joints from a wide range of developmental stages, we demonstrate that the morphological abnormalities that result from embryonic immobilization are associated with altered patterns of tenascin-C and collagen-XII expression within developing joint structures. As the joints fuse in immobilized embryos, the cells of the presumptive articular surface differentiate from flattened fibroblasts to more rounded chondrocytes and collagens XII and I are no longer detected at sites of complete joint fusion. Although the expression of collagen XII persists at normal levels elsewhere within the immobilized joint, tenascin-C expression is diminished within the chondroepiphysis, synovium, and tendons, as well as within the remains of the fibrous articular surface. This effect is most notable for the shortest tenascin variant (Tn190) within the chondroepiphysis and the largest variant (Tn230) within tendons, synovium, and the fibrous surface layer of the joint. This study thus provides in vivo support of previous in vitro work that suggests that tenascin expression is sensitive to external changes in mechanical loading environment. However, these data do not support a similar conclusion for collagen XII during early development.

Animals↗

Cell-type-specific nuclear translocation of fibroblast growth factor-2 isoforms during chicken kidney and limb morphogenesis.

Analysis of the fibroblast growth factor-2 (FGF-2 or bFGF) proteins during chicken embryonic pattern formation and organogenesis revealed that three isoforms (18.5, 20.0, and 21.5 kDa) were synthesized by alternative translation initiation from one coding region. A highly specific antiserum was raised and used for studying the temporal and spatial distribution of the FGF-2 isoforms during chicken embryogenesis. The distribution of FGF-2 proteins during limb pattern formation has been unraveled. Their presence in both ectodermal and mesenchymal cells is consistent with an involvement in regulating the balance of growth and differentiation. High levels of FGF-2 proteins were furthermore detected in all epithelial cells of the developing kidney from the pronephric stage onward. The proteins were in general predominantly cytoplasmic, but a specific subpopulation of limb mesenchymal cells and kidney epithelial cells (podocytes) showed a striking nuclear localization. Nuclear translocation of the FGF-2 proteins occurred in differentiating podocytes of meso- and metanephric glomeruli and was maintained in adult kidneys. These results, in contrast to previous in vitro studies, revealed that nuclear accumulation of FGF-2 proteins is restricted to few specific cells during embryogenesis.

Amino Acid Sequence↗

Does quasi-local competition lead to pattern formation in metapopulations? An explicit resource competition model.

In metapopulations, competitive interactions may extend beyond the confines of the local population such that members of neighbouring habitat patches affect each other adversely (quasi-local competition). We derive a model for quasi-local competition from first principles, assuming that individuals compete for shared resources and members of a population spend a certain fraction of their foraging time in the adjacent populations. Contrary to the results of Doebeli and Killingback [2003. Theor. Popul. Biol. 64, 397-416], our model does not produce spatial patterns of population densities in homogeneous environments. Quasi-local competition nevertheless contributes to pattern formation by amplifying the effect of heterogeneities in the external environment, and this amplification can be extremely strong when dispersal is absent. We discuss why apparently similar models lead to contrasting results.

Competitive Behavior↗