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A Gierer

Publications and source records attributed to A Gierer.

At least 19 recordsLinked to original sources
PubMed2000

Pattern formation by local self-activation and lateral inhibition.

In 1972, we proposed a theory of biological pattern formation in which concentration maxima of pattern forming substances are generated through local self-enhancement in conjunction with long range inhibition. Since then, much evidence in various developmental systems has confirmed the importance of autocatalytic feedback loops combined with inhibitory interaction. Examples are found in the formation of embryonal organizing regions, in segmentation, in the polarization of individual cells, and in gene activation. By computer simulations, we have shown that the theory accounts for much of the regulatory phenomena observed, including signalling to regenerate removed parts. These self-regulatory features contribute to making development robust and error-tolerant. Furthermore, the resulting pattern is, to a large extent, independent of the details provided by initial conditions and inducing signals.

Animals↗
PubMed1998

Possible involvement of gradients in guidance of receptor cell axons towards their target position on the olfactory bulb.

There is increasing evidence for directional guidance of growing axons by molecular gradients in target tissues. Aside from biochemical studies on gradients and their role, the capability of axons to approach their target position from different aspects of a two-dimensional field is itself an indication for guidance by gradients. According to this criterion, such guidance is expected to be involved not only in map-formation in the visual system but also in targeting of receptor cell axons in the olfactory bulb. In this paper, physico-chemical concepts of visual mapping are adapted to olfactory targeting. In both cases there must be sophisticated processing of graded cues in the growing tip of the axon for growth cone navigation. In visual map formation, a target position is determined by influences of cues depending on the position of axonal origin; in olfactory targeting, however, these influences are expected to be based on properties of the receptor-cell-specific molecules (possibly including the receptor molecule itself), as well as by gene regulation affecting the levels of expression. According to this concept, the main role of molecules expressed in a receptor-cell-type specific manner is not matching specific counterparts on the target tissue, but instead quantitative modulation of growth cone steering for sensing the direction towards the target position.

Animals↗
PubMed1995

Development of layers, maps and modules.

Developing neuronal cell sheets acquire position-specific features by mechanisms that differ in radial and tangential dimensions. These features include guiding cues for axonal growth and targeting that are used, for example, in map formation. Recent evidence supports the notion that graded distributions of molecules are involved in growth cone navigation and axonal branching. In addition, activity-dependent processes are important determinants of functional architecture, especially with respect to modular organization.

Afferent Pathways↗
PubMed1988

Spatial organization and genetic information in brain development.

In the course of brain development neurons acquire qualitative and quantitative biochemical and morphological properties which depend on the position of the cells within the nervous system. In the dimensions tangential to multilayered cell sheets mechanisms contributing to spatial order include induction by adjacent tissue as well as internal generation of morphogenetic fields (presumably by reactions involving autocatalysis and lateral inhibition). In the dimensions across the sheet cells of different types are produced in one layer and sort into another layer, guided presumably by contact mediated cell interaction. Positional and directional cues encoded in the developing brain are essentially involved in axonal guidance and the formation of neuronal connections. In mammals and man, the number of neurons and their connections in the brain is much higher than the number of genes. This is possible because there are repetitive neuronal circuits in the brain, and there is topographic order of connections between different brain areas. For instance, few quantitatively graded markers would suffice for specifying the projection of one area of the nervous system onto another, generating spatial order for a large number of fibers while requiring only a limited amount of genetic information. Higher brain functions, such as learning and memory, may logically require only a neural network consisting of repetitive subunits. On the other hand, it is an evolutionary advantage for an organism to be endowed, from the outset, with a pattern of neural connections which is subtly and quantitatively tuned for efficiency in dealing with the environment, while remaining flexible for change and adaptation in the course of learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1984

Reaggregation of embryonic chick retina cells: pigment epithelial cells induce a high order of stratification.

We report here that, in comparison to aggregates from retinal cells alone, addition of pigmented epithelial cells to retinal cells in rotary culture results in a pronounced increase of spatial order. A particularly high level of organization is found in about 15-20% of the aggregates. In these 'retinoids' the main layers characteristic of developing in vivo retinae can be distinguished in correct sequential arrangement on the basis of morphological criteria and by using acetylcholinesterase histochemistry [5, 6, 15], peanut agglutinin-lectin binding [11] and Lucifer Yellow staining [7-9].

Acetylcholinesterase↗
PubMed1983

Model for the retino-tectal projection.

A model for the retino-tectal projection is proposed which assumes that axonal growth proceeds predominantly in the direction of maximal slope of a guiding substance (or, more generally, of a system parameter subsuming the effect of several substances). The spatial distribution of this parameter, in turn, results from the interaction of components of retinal axons (which are graded with respect to position of origin in the retina) and tectal components. One or two gradients in each dimension of retina and tectum suffice. Conditions for the generation of a reliable projection on this basis are relatively simple and consistent with conventional enzyme and receptor kinetics. Adhesive forces could but need not be involved in the guiding mechanism. The slope of guiding substances that interfere with an intracellular pattern-forming mechanism within the growth cone may determine the polarity of activation and thus the direction of growth. Generation of primary projections and some features of regulation such as independence of projections on neural pathways, and observations on the innervation of rotated pieces of tectum, can be explained on the basis of the model. The model can be extended by introducing additional production of guiding substance depending on the density, and duration of presence, of fibre terminals in the course of innervation. This simple mechanism would suffice for observed effects of compression and expansion of the map following ablation of retinal and tectal tissue, respectively. It may but need not be involved in the primary projection, too.

Animals↗
PubMed1983

Binding of FITC-coupled peanut-agglutinin (FITC-PNA) to embryonic chicken retinas reveals developmental spatio-temporal patterns.

FITC-labeled peanut agglutinin (PNA), a lectin from peanut (Arachis hypogaea) which binds specifically to D-galactose, was used as a probe to trace the distribution of PNA-lectin receptors during early development of chick retina. We found that specific fluorescence within the inner plexiform layer (IPL) and the outer plexiform layer (OPL) appears at different developmental stages. The specific fluorescence of the IPL first appears near the central area of the ventro-posterior quadrant of the 7-day retina, then extends progressively towards the periphery, reaching the ora serrata earlier on the posterior than on the anterior side. The development of the specific fluorescence of the OPL follows the same scheme, but it appears later (starting at day 9) than that of the IPL and it is less pronounced. The spatio-temporal patterns of the expression of the lectin receptors show relationships to those of withdrawal of proliferating cells from mitosis, and of other events related to differentiation.

Animals↗
PubMed1983

Self-renewal of stem cells and differentiation of nerve cells in the developing chick retina.

Data on proliferation and self-renewal of stem cells in the developing chick retina were obtained on the basis of measurements of cells labeled by [3H]thymidine pulses in conjunction with the rate of increase in total cell number. Duration of S-phase was found to be about 4 h between stages 4 and 9 days. Self-renewal drops below the critical value of 50% (implying a transition from increase to depletion of absolute number of stem cells in the tissue) around day 7.6. The spatial order of cell proliferation was studied by measurements taken on subregions of retinas at various stages of development. Proliferating cells forming the ventricular layer increase in all regions of the retina up to day 7, though the proportion of proliferating cells is lowest in the center. From day 5 on it is higher in the nasal as compared to the temporal part of the tissue. After day 7 self-renewal of stem cells drops below 50%, stem cells become depleted and withdraw gradually from mitosis. The process is initiated in the center slightly temporal to the dorsal end of the optic fissure and then spreads rapidly towards the periphery, reaching the temporal margin first. The findings imply that while cells at the periphery are younger on the average, those cells which have become postmitotic at an early stage are not confined to a small central core of the fully developed retina, because the tissue continues to grow and produce postmitotic cells in all regions of the retina up to day 7.

Animals↗
PubMed1981

Some physical, mathematical and evolutionary aspects of biological pattern formation.

An important mechanism in the generation of biological structures is the production of defined spatial patterns within initially near-uniform cells and tissues. This process can be modelled on the basis of conventional molecular kinetics if there is a short-range activating effect in conjunction with depletion or inhibition extending over a wider range ('lateral inhibition'). Such pattern-generating systems exhibit simple self-regulatory properties empirically observed in developmental biology such as polarity effects, proportion regulation and the inducibility of secondary centres. Autocatalysis and lateral inhibition have been shown to be mathematically necessary for the simplest two-factor case. Certain generalizations of these conditions to multi-component systems are possible; they are suitable for modelling intercalary regeneration. The evolution of higher organisms seems to be determined to a considerable extent by many small changes of patterns and proportions. While evolution proceeds at varying rates in the course of time, the rate-limiting steps may be due to mutations of low selection pressure. A semi-quantitative argument suggests that there might be an upper limit of evolutionarily effective genetic complexity.

Animals↗
PubMed1981

Development of projections between areas of the nervous system.

A theory of projections in the nervous system (such as the retino-tectal projection) is proposed. Components of axonal growth cones and target tissue interact and cooperate, within the area of contact, to generate a guiding parameter, in the simplest case a "guiding substance" of distribution p. The components which are involved in this production are assumed to have graded distributions with respect to position in the projecting and target area, respectively. The distribution p thus produced guides the growth cone in the direction of maximal slope until the minimal value of p is reached. In this way, each growth cone can be guided to a position on the target tissue which depends on the origin of the fiber in such a manner that a projection results. Adhesive forces could but need not be involved in the guiding mechanism. The slope of p may interfere with an intracellular pattern forming mechanism within the growth cone, determining the polarity of activation (as modelled previously on the basis of autocatalysis and lateral inhibition) and thus the direction of growth. For the generation of a distribution of p leading to a reliable projection, simple graded distributions in the projecting and target area suffice, involving one or two components in each dimension. Their effect on the generation of p may be activatory as well as inhibitory. Exponential gradients give rise to particularly simple mapping functions. The following is an example of this general type of model: Growth cones as well as target tissue contribute to the production of a guiding substance. For each dimension, there is, in the target tissue, an exponentially graded component exerting (directly or indirectly) two functions: it actively produces guiding substance p and it interacts, in an inhibitory fashion, with the production of p by a component of the growth cone (which is, in turn, graded with respect to position of origin in the projecting area). While the theory is proposed as a fair approximation of the primary events in neural projections, superimposed regulatory effects can also be incorporated. These include fiber-fiber interactions, mechanisms smoothing out unequal density distributions of axon terminals and effects of time of arrival of fibers on the projection, which have been proposed previously as primary mechanisms generating projections. A further extension of the model is to assume that crude and more refined positional specificity is determined in a combinatorial fashion, allowing the possibility of interchanges and transformations of parameters.

Animals↗
PubMed1981

[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↗
PubMed1981

Separation of cell subpopulations from embryonic chick neural retina with fluorescence-activated cell sorting.

Fluorescence-activated cell analysis and sorting was used to characterize and separate cell subpopulations from the developing chick retina according to size, stage in the cell cycle and location in the tissue. It was shown that uptake of rhodamine B isothiocyanate (RITC) protein stain, light-scattering at large angles, and the time of flight of cells through the laser beam all correlate with cell size. Vital staining of DNA by H33342 permits cell separation according to phase in the cell cycle (G1, S, G2 + M). Further, a method was developed for separating postmitotic cells, based upon the quenching of H33342 fluorescence by the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into DNA. Quantitative data reflect the decrease of DNA-synthesizing cells and the increase of postmitotic cells as the development of the retina proceeds. Isolation of cells on the basis of their location in the whole tissue is achieved by exposing the desired surface (e.g. the inner (concave) surface of the retina, which is rich in ganglion cells) to a suspension of Fluorescamine, which stains only cell layers close to the surface. Sorting out the fluorescing cells yields a high proportion of cells with the appearance, size and postmitotic characteristics of ganglion cells.

Animals↗
PubMed1981

Cholera-toxin binding to cells of developing chick retina analyzed by fluorescence-activated cell sorting.

The occurrence of gangliosides on nerve cells of the developing retina was studied by fluorescence-activated cell analysis and sorting, using fluorescent cholera toxin as marker. This toxin binds to GM1; neuraminidase converts several other gangliosides into GM1. Without pretreatment by this enzyme weak binding of toxin is detected at later stages of development, whereas pretreatment leads to considerable toxin binding at earlier stages. The number of cells binding toxin as well as the amount bound per cell increase with developmental age of the retina. Cells binding a given amount of toxin vary strongly in size. Cell sorting was used to separate postmitotic cells from proliferating cells. Proliferating cells have little binding capacity, while postmitotic cells bind relatively large amounts of toxin. Localization of gangliosides which bind toxin in the developing retina was studied in cryostat sections. At an early stage (day 6) toxin binding is localized in the inner layer of the developing retina which contains the ganglion and other postmitotic cells, but is not found in the outer layer of matrix cells. At later stages complex staining patterns evolve with binding predominantly in the nerve fiber layers.

Animals↗