A boundary model for pattern formation in vertebrate limbs

Development ◽  
1983 ◽  
Vol 76 (1) ◽  
pp. 115-137
Author(s):  
Hans Meinhardt
Keyword(s):  
Pattern Formation ◽  
Positional Information ◽  
Cell Types ◽  
Cooperative Interaction ◽  
Main Body ◽  
Polar Coordinate ◽  
Coordinate Model ◽  
Supernumerary Limbs ◽  
Boundary Model

We postulate that positional information for secondary embryonic fields is generated by a cooperative interaction between two pairs of differently determined cell types. Positional information is thus generated at the boundaries between cells of different determination. The latter are assumed to result from the primary pattern formation in the embryo. The application of this model to vertebrate limbs accounts for the pairwise determination of limbs at a particular location, with a particular handedness and alignment to the main body axes of the embryo. It accounts further for the gross difference in the regeneration of double anterior and double posterior amphibian limbs as well as for the formation of supernumerary limbs after certain graft experiments including supernumeraries in which the dorsoventral polarity changes or which consist of two anterior or two posterior halves. Our model provides a feasible molecular basis for the polar coordinate model and successfully handles recently found violations, for instance formation of supernumerary limbs after ipsilateral grafting with 90° rotation. The most frequent types of developmental malformations become explicable. The models allow specific predictions which are fully supported by recent experiments (see the accompanying paper of M. Maden).

Regeneration in the anterior—posterior axis of the insect thoracic segment

Development ◽  
1986 ◽  
Vol 98 (1) ◽  
pp. 137-165
Author(s):  
Vernon French ◽  
Tamara F. Rowlands
Keyword(s):  
Abdominal Segment ◽  
Adjacent Tissue ◽  
Local Pattern ◽  
Shortest Route ◽  
Polar Coordinate ◽  
Coordinate Model ◽  
Deletion Pattern ◽  
Boundary Model ◽  
Third Line ◽  
Anterior Posterior

After removal of a transverse strip of ventral thorax from the beetle, Tenebrio molitor, interaction occurred between epidermis posterior to the mesothoracic leg and that anterior to the metathoracic leg. Depending on the size and position of the excision, this interaction resulted in either the regeneration of the extirpated tissue or its replacement by an A/P reversed pattern of sclerites and supernumerary leg. By either route, local pattern continuity was restored between the normal meso- and metathoracic legs. Similarly, when a leg plus adjacent tissue was extirpated, continuity was restored by leg regeneration or by formation of an A/P reversed duplication of sclerites. The results of these strip excisions can be understood in terms of two current models of the ventral thorax (the Boundary Model and the Polar Coordinate Model), each of which postulates a distinct compartment or region intervening between the epidermis surrounding the bases of successive legs. However, the models do not explain the large differences in the frequency of formation of the duplication/deletion pattern after excisions of different widths. The results are also compatible with a different model, involving an A–P sequence of positional values similar to that proposed for the abdominal segment. Regeneration would restore continuity within the sequence by the shortest route, forming either the midsegment (including the leg) or the intersegmental region. The meso- and metathorax differ in the structure of the ventral sclerites and in the segmentation of the tarsus of the leg. The structures regenerated after the various excisions show that the segment border is not crossed during regeneration and indicate that an A/P compartment border running through the leg is usually also respected. There is no sign, however, of a third line of lineage restriction that would indicate a subdivision of the segment into three compartments (as proposed in the Boundary Model).

Applications of a Theory of Biological Pattern Formation Based on Lateral Inhibition

1974 ◽  
Vol 15 (2) ◽  
pp. 321-346 ◽  
Author(s):  
H. MEINHARDT ◽  
A. GIERER
Keyword(s):  
Pattern Formation ◽  
Lateral Inhibition ◽  
Molecular Mechanisms ◽  
Positional Information ◽  
Cell Types ◽  
Model Calculations ◽  
Slime Moulds ◽  
Biological Pattern Formation ◽  
Pattern Forming ◽  
Differentiation And Proliferation

Model calculations are presented for various problems of development on the basis of a theory of primary pattern formation which we previously proposed. The theory involves short-range autocatalytic activation and longer-range inhibition (lateral inhibition). When a certain criterion is satisfied, self-regulating patterns are generated. The autocatalytic features of the theory are demonstrated by simulations of the determination of polarity in the Xenopus retina. General conditions for marginal and internal activation, and corresponding effects of symmetry are discussed. Special molecular mechanisms of pattern formation are proposed in which activator is chemically converted into inhibitor, or an activator precursor is depleted by conversion into activator. The (slow) effects of primary patterns on differentiation can be included into the formalism in a straightforward manner. In conjunction with growth, this can lead to asymmetric steady states of cell types, cell differentiation and proliferation as found, for instance, in growing and budding hydra. In 2 dimensions, 2 different types of patterns can be obtained. Under some assumptions, a single pattern-forming system produces a ‘bristle’ type pattern of peaks of activity with rather regular spacings on a surface. Budding of hydra is treated on this basis. If, however, gradients develop under the influence of a weak external or marginal asymmetry, a monotonic gradient can be formed across the entire field, and 2 such gradient-forming systems can specify ‘positional information’ in 2 dimensions. If inhibitor equilibrates slowly, a spatial pattern may oscillate, as observed with regard to the intracellular activation of cellular slime moulds. The applications are intended to demonstrate the ability of the proposed theory to explain properties frequently encountered in developing systems.

Pattern formation and growth in the regenerating limbs of urodelean amphibians

Development ◽  
1981 ◽  
Vol 65 (Supplement) ◽  
pp. 19-36
Author(s):  
Nigel Holder
Keyword(s):  
Quantitative Analysis ◽  
Pattern Formation ◽  
Limb Regeneration ◽  
Polar Coordinate ◽  
Coordinate Model ◽  
Pattern Regulation

The results of numerous types of grafting experiments involving the amputation of symmetrical limbs are described. These experiments were designed to test the tenets of the polar coordinate model. The analysis of the results of these grafts coupled with a quantitative analysis of blastemal shape strongly indicates that pattern regulation during amphibian limb regeneration can be understood in terms of the model.

Regeneration in the medial-lateral axis of the insect thoracic segment

Development ◽  
1988 ◽  
Vol 102 (1) ◽  
pp. 175-192
Author(s):  
V. French ◽  
T.F. Rowlands
Keyword(s):  
Mirror Image ◽  
The Body ◽  
Dorsal Midline ◽  
Unequally Spaced ◽  
Polar Coordinate ◽  
Coordinate Model ◽  
Boundary Model ◽  
Almost All ◽  
Pattern Regulation ◽  
Lateral Axis

We have studied pattern regulation in the medial-lateral axis of the insect segment by grafting legs of beetle larvae (Tenebrio molitor) in different orientations into different positions medial and lateral to the leg site. The Boundary Model and Polar Coordinate Model of the insect appendage predict various patterns of supernumerary leg regeneration, and these grafts were designed to test the predictions. When a larval leg is grafted with normal anterior-posterior orientation medial to the normal leg, larvae and subsequent adults bear the graft plus a supernumerary leg. This is located where the lateral edge of the grafted leg confronted medial thorax (from the leg base across to the midline) and is orientated as a mirror image of the graft. The tarsal structure of supernumeraries resulting from grafts of the mesothoracic leg onto the metathorax shows that the supernumeraries may be derived from the graft, the host site or from both sources. Similarly, when a leg is grafted lateral to the leg site, a supernumerary forms at the confrontation between the medial edge of the graft and lateral thorax (from leg base across to the dorsal tergite). These results agree with the predictions of both models and would indicate that the compartments or the positional values extend out from the leg to the midline and the edge of the tergite. The two models differ in their predictions for the number, position and orientation of supernumeraries following 180 degree rotation of the grafted leg. When the rotated graft is placed lateral to the leg, larvae and adults form a single supernumerary which, in accordance with the Polar Coordinate Model, is lateral to the graft and orientated as a mirror image of it. However, the results of the corresponding medial graft cannot be readily explained by either model. Larvae form a single supernumerary either posterior or medial to the graft, suggesting a modified model with unequally spaced positional values, but the subsequent adult supernumeraries are almost all located medially. Experiments involving a graft placed medial to the leg site frequently show duplication of the adult midline suture, an extra branch forming between the thorax and the graft or supernumerary leg. In this case, as in the regeneration of the dorsal midline, the extreme medial structure is formed between two more lateral regions, which need not come from opposite sides of the body, but must have opposite mediolateral polarities. At present, no model can adequately explain all the results of grafting and extirpation on the insect ventral thorax.

Maintenance and regulation of cellular handedness in Tetrahymena

Development ◽  
1989 ◽  
Vol 105 (3) ◽  
pp. 457-471
Author(s):  
E.M. Nelsen ◽  
J. Frankel
Keyword(s):  
Positional Information ◽  
Mirror Image ◽  
Local Geometry ◽  
Preferred Direction ◽  
Left Handed ◽  
Polar Coordinate ◽  
Nuclear Events ◽  
Coordinate Model ◽  
Lh Cells ◽  
Lh Rh

The left-handed phenotype of Tetrahymena thermophila (LH) is a global mirror image of its right-handed counterpart (RH). LH cells are ‘wound’ in the opposite direction from that of RH cells with respect to the placement of all structures that are asymmetrically disposed on the cell circumference. However, the local geometry of ciliary rows, including the asymmetrically placed microtubule bands and other accessory structures, is identical in RH and LH cells. Populations of LH cells grow more slowly than those of RH cells, probably because of nutritional problems due to faulty construction of the cell mouth. LH cells, like RH cells, conjugate in a homopolar configuration, while LH cells mate with RH cells in a heteropolar union which suffices to initiate the conjugal nuclear events but is insufficient to allow survival of progeny. Subclonal analyses indicate that reversion of the LH to the RH form is relatively rare. However, the frequency of reversion is greatly increased by conditions that promote the formation of doublets by fission arrest. An analysis of intermediate doublet forms in such cultures strongly suggests that reversion takes place through a specific pathway, with LH-LH doublets regulating to LH-RH forms that then may give rise to RH singlets. The origin and fate of the LH-RH intermediate forms can be explained by applying a modified polar coordinate model of positional information with the proviso that there is a preferred direction for the intercalation of new positional values.

scholarly journals ECM-mediated positional cues are able to induce pattern, but not new positional information, during axolotl limb regeneration

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248051
Author(s):  
Warren A. Vieira ◽  
Shira Goren ◽  
Catherine D. McCusker
Keyword(s):  
Pattern Formation ◽  
Connective Tissue ◽  
Limb Regeneration ◽  
Positional Information ◽  
Cell Types ◽  
Induce Pattern ◽  
Tissue Cells ◽  
Pattern Information

The Mexican Axolotl is able to regenerate missing limb structures in any position along the limb axis throughout its life and serves as an excellent model to understand the basic mechanisms of endogenous regeneration. How the new pattern of the regenerating axolotl limb is established has not been completely resolved. An accumulating body of evidence indicates that pattern formation occurs in a hierarchical fashion, which consists of two different types of positional communications. The first type (Type 1) of communication occurs between connective tissue cells, which retain memory of their original pattern information and use this memory to generate the pattern of the regenerate. The second type (Type 2) of communication occurs from connective tissue cells to other cell types in the regenerate, which don’t retain positional memory themselves and arrange themselves according to these positional cues. Previous studies suggest that molecules within the extracellular matrix (ECM) participate in pattern formation in developing and regenerating limbs. However, it is unclear whether these molecules play a role in Type 1 or Type 2 positional communications. Utilizing the Accessory Limb Model, a regenerative assay, and transcriptomic analyses in regenerates that have been reprogrammed by treatment with Retinoic Acid, our data indicates that the ECM likely facilities Type-2 positional communications during limb regeneration.

Pattern formation in Dictyostelium discoideum

Development ◽  
1977 ◽  
Vol 40 (1) ◽  
pp. 229-243
Author(s):  
D. Forman ◽  
D. R. Garrod
Keyword(s):  
Life Cycle ◽  
Pattern Formation ◽  
Single Cells ◽  
Cell Mass ◽  
Positional Information ◽  
Cell Types ◽  
Immunofluorescent Staining ◽  
Cell Contact ◽  
Slime Mould ◽  
Normal Life

Cells of the cellular slime mould D. discoideum were allowed to form into spherical aggregates, by shaking vegetative cells as a suspension in phosphate buffer. In such conditions, grex polarity is never established and surface sheath is not formed (Loomis, 1975 a). Despite the absence of such characteristics of normal development, differentiation of prespore cells, as tested for by immunofluorescent staining, and the organization of such cells into a patterned structure still occurred within the aggregates. Differentiation of prespore cells was found to occur within the cultures at times equivalent to those in the normal life cycle; such differentiation could be advanced by pulsation of the cultures with cyclic-AMP. When cell contact and aggregate formation was prevented, differentiation never occurred within the single cells. Our results suggest that the prespore cells develop randomly within the aggregate and that a pattern is subsequently formed as a result of sorting out of cell types within the cell mass. Aggregates shaken for extended periods of time showed development into cyst-like structures. The process of pattern formation that occurred within these aggregates which possess neither polarity nor a grex tip, would be unlikely to involve any mechanism of positional information signalling. The relevance of polar organization in the generation of pattern in the normal life cycle may therefore be questionable. We present a model of pattern formation in the slime mould in which sorting out of predetermined cell types is viewed as the major mechanism in bringing about patterned organization of the grex precursor cells.

par-4, a gene required for cytoplasmic localization and determination of specific cell types in Caenorhabditis elegans embryogenesis.

Genetics ◽  
1992 ◽  
Vol 130 (4) ◽  
pp. 771-790 ◽  
Author(s):  
D G Morton ◽  
J M Roos ◽  
K J Kemphues
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Types ◽  
Intestinal Cells ◽  
Specific Cell ◽  
Cytoplasmic Localization ◽  
Loss Of Function ◽  
Embryo Viability ◽  
Cell Stage ◽  
Maternal Genome

Abstract Specification of some cell fates in the early Caenorhabditis elegans embryo is mediated by cytoplasmic localization under control of the maternal genome. Using nine newly isolated mutations, and two existing mutations, we have analyzed the role of the maternally expressed gene par-4 in cytoplasmic localization. We recovered seven new par-4 alleles in screens for maternal effect lethal mutations that result in failure to differentiate intestinal cells. Two additional par-4 mutations were identified in noncomplementation screens using strains with a high frequency of transposon mobility. All 11 mutations cause defects early in development of embryos produced by homozygous mutant mothers. Analysis with a deficiency in the region indicates that it33 is a strong loss-of-function mutation. par-4(it33) terminal stage embryos contain many cells, but show no morphogenesis, and are lacking intestinal cells. Temperature shifts with the it57ts allele suggest that the critical period for both intestinal differentiation and embryo viability begins during oogenesis, about 1.5 hr before fertilization, and ends before the four-cell stage. We propose that the primary function of the par-4 gene is to act as part of a maternally encoded system for cytoplasmic localization in the first cell cycle, with par-4 playing a particularly important role in the determination of intestine. Analysis of a par-4; par-2 double mutant suggests that par-4 and par-2 gene products interact in this system.

scholarly journals Multiplexed Plasmonic Nano-Labeling for Bioimaging of Cytological Stained Samples

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3509
Author(s):  
Paule Marcoux-Valiquette ◽  
Cécile Darviot ◽  
Lu Wang ◽  
Andrée-Anne Grosset ◽  
Morteza Hasanzadeh Kafshgari ◽  
...  
Keyword(s):  
Accurate Determination ◽  
Cell Types ◽  
Fine Needle Biopsy ◽  
Dark Field ◽  
Imaging Method ◽  
New Methods ◽  
Formalin Fixed Paraffin ◽  
Dark Field Microscopy ◽  
Formalin Fixed Paraffin Embedded

Reliable cytopathological diagnosis requires new methods and approaches for the rapid and accurate determination of all cell types. This is especially important when the number of cells is limited, such as in the cytological samples of fine-needle biopsy. Immunoplasmonic-multiplexed- labeling may be one of the emerging solutions to such problems. However, to be accepted and used by the practicing pathologists, new methods must be compatible and complementary with existing cytopathology approaches where counterstaining is central to the correct interpretation of immunolabeling. In addition, the optical detection and imaging setup for immunoplasmonic-multiplexed-labeling must be implemented on the same cytopathological microscope, not interfere with standard H&E imaging, and operate as a second easy-to-use imaging method. In this article, we present multiplex imaging of four types of nanoplasmonic markers on two types of H&E-stained cytological specimens (formalin-fixed paraffin embedded and non-embedded adherent cancer cells) using a specially designed adapter for SI dark-field microscopy. The obtained results confirm the effectiveness of the proposed optical method for quantitative and multiplex identification of various plasmonic NPs, and the possibility of using immunoplasmonic-multiplexed-labeling for cytopathological diagnostics.

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