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1.
Retinoic acid proximalizes level-specific properties responsible for intercalary regeneration in axolotl limbs 总被引:2,自引:0,他引:2
The objective of this study was to determine whether retinoic acid (RA) coordinately proximalizes positional memory and the cellular recognition system that detects pattern discontinuity in regenerating amphibian limbs. The strategy was to test the capacity of RA-treated blastemas to evoke intercalary regeneration when grafted to an amputation level proximal to their level of origin. Control wrist and ankle, or elbow and knee blastemas treated with the retinoid solvent, dimethylsulphoxide, evoked intercalary regeneration as effectively as untreated blastemas, when grafted to the midstylopodial amputation surface of host limbs. RA-treated wrist and ankle or elbow and knee blastemas were proximalized and formed complete limbs that were at an angle to, or continuous with, the midstylopodium of the host limb. No intercalary regeneration, from either graft or host, was observed in these cases. The results indicate that the cellular mechanism that recognizes disparities between non-neighbouring cells and initiates intercalary regeneration is coordinately proximalized with positional memory. Thus the recognition mechanism and positional memory are directly related. Intercalary regeneration and corrective displacement (affinophoresis), both of which restore a pattern of normal cell neighbours by different means in regenerating axolotl limbs, appear to use the same mechanism to recognize pattern discontinuity. 相似文献
2.
Summary Studies on intercalary regeneration in several organisms have shown that a regenerate is formed when surfaces of different positional value along the proximo-distal axis are opposed. One of the main problems posed by this phenomenon is to know which piece contributes to the building of the regenerate. In the present work we have studied this problem in planarians using chimaeras made between pieces of different body levels, irradiated or not, of the sexual and asexual races ofDugesia(S)mediterranea that differ in a chromosomal marker.The results found show very clearly that intercalary regenerates in planarians are formed by cells coming from both pieces (stumps), and that irradiated pieces keep the positional values and interact with non-irradiated pieces to restore the missing parts. This means that distal and proximal transformation do actually occur at the same time during intercalary regeneration in planarians. The implications of these results as regards to the origin of cells in the regenerate and to present models of intercalary regeneration are discussed. 相似文献
3.
SYNOPSIS. Developing insect legs have positional informationspecified down the length and around the leg circumference.After grafting or amputation of larval cockroach or cricketlegs healing confronts epidermal cells with different positionalvalues. This stimulates growth, the intercalary regenerationof intervening tissue, the regeneration of all more distal tissuefrom a complete leg circumference and often the formation ofan incomplete distal regenerate from a symmetrical part-circumference.These processes will lead to regeneration of missing structures,duplication of structures, or the formation of branched supernumerarylegs, depending on the situation. During regeneration, cellscannot cross lineage restrictions which divide the leg intoanterior and posterior compartments. 相似文献
4.
Cell interactions and regeneration control 总被引:1,自引:0,他引:1
B Boilly E Lheureux Y Boilly-Marer A Bart 《The International journal of developmental biology》1990,34(1):219-231
This paper is a review of the main findings of our laboratory on the control of regeneration by cell interactions. These include results related to the role of both cell contact and local soluble factors in regeneration of the legs of insects and newts and of the parapodia and segments of nereis. The pattern of these structures is considered to be defined by positional information distributed as longitudinal and transverse positional value sequences carried by epidermal (insect) or mesenchymal (newt) cells. By associating tissues to create transverse and longitudinal discontinuities in these sequences, single or multiple regenerating structures were obtained. These structures are formed by the intercalation of cells characterized by intermediate positional values which fill the gap between the tissues in contact. Positional information may also be changed during regeneration by the nerve cord in nereis and retinoids in the newts. We describe additional cases where morphogenesis occurs without any overt discontinuity in positional information, such as from a locally injured or non-injured insect trochanter, or after deflection of nerves in nereis and newt. Regeneration following an amputation may be considered as a special case of intercalary regeneration, the first stage being the juxtaposition of normally non-contiguous cells resulting in a longitudinal or/and a transverse gap. We also report studies on local factors produced by nerves and the blastema during newt limb regeneration. The nerve factor is necessary for the division of blastemal cells. After denervation, mesenchyme differentiates in an abnormal way. The mitogenic signal from the nerves is mediated by the PKC pathway. Its production is enhanced by regeneration of cut nerve fibers. The blastema also produces growth factors. We show that the epidermal cap and mesenchyme contain acidic FGF-like factor, and that the proliferating mesenchyme stimulates nerve fibers to regrow into the blastema. 相似文献
5.
John L. Haynie 《Development genes and evolution》1982,191(5):293-300
Summary The regulative behavior of fragments of the imaginal discs of the wing and first leg was studied when these fragments were combined with fragments of other thoracic imaginal discs. A fragment of the wing disc which does not normally regenerate when cultured could be stimulated to regenerate by combination with certain fragments of the haltere disc. When combined with a haltere disc fragment thought to be homologous by the criteria of morphology and the pattern of homoeotic transformation, such stimulated intercalary regeneration was not observed. Combinations of first and second leg disc fragments showed that a lateral first leg fragment could be stimulated to regenerate medial structures when combined with a medial second leg disc fragment but not when combined with a lateral second leg disc fragment. Combinations of wing and second leg disc fragments showed that one fragment of the second leg disc is capable of stimulating regeneration from a wing disc fragment while another second leg disc fragment fails to stimulate such regeneration. It is suggested that absence of intercalary regeneration in combinations of fragments of different thoracic imaginal discs is a result of homology or identity of the positional information residing in the cells of the fragments. The pattern of correspondence of positional information revealed by this analysis is consistant with the pattern of homology determined by morphological observation and by analysis of the positional specificity of homoeotic transformation among serially homologous appendages. The implications of the existence of homologous positional information in wing and second leg discs which share a common cell lineage early in development are discussed. 相似文献
6.
Nakamura T Mito T Tanaka Y Bando T Ohuchi H Noji S 《Development, growth & differentiation》2007,49(2):79-88
The cricket Gryllus bimaculatus is a hemimetabolous insect whose nymphs possess the ability to regenerate amputated legs. Previously, we showed that Gryllus orthologues of Drosophila hedgehog (Gb'hh), wingless (Gb'wg) and decapentaplegic (Gb'dpp) are expressed during leg regeneration and play essential roles in the establishment of the proximal-distal axis. Here, we examined their roles during intercalary regeneration: when a distally amputated tibia with disparate positional values is placed next to a proximally amputated host, intercalary growth occurs in order to regenerate the missing part. In this process, we examined expression patterns of Gb'hh and Gb'wg. We found that expressions of Gb'hh and Gb'wg were induced in a regenerate and the host proximal to the amputated region, but not in the grafted donor distal to the regenerate. This directional induction occurs even in the reversed intercalation. Because these results are consistent with a distal-to-proximal respecification of the regenerate, Gb'wg may be involved in the re-establishment of the positional values in the regenerate. Furthermore, we found that no regeneration occurs when Gb'armadillo (the orthologue of beta-catenin) was knocked down by RNA interference. These results indicate that the canonical Wnt/Wingless signaling pathway is involved in the process of leg regeneration and determination of positional information in the leg segment. 相似文献
7.
We have tested the ability of fragments of one type of imaginal disc to stimulate regeneration of another type. It has been shown by others that, when extreme proximal and distal fragments of the wing disc are combined, intercalary regeneration of the missing tissue ensues. Each fragment, if cultured alone, will merely duplicate its structures. We now find that distal fragments of other thoracic discs, haltere and leg, while retaining their autonomy for differentiation, also interact with proximal wing tissue to promote regeneration of more distal wing structures. The proximal wing tissue used in these experiments was the wingless abnormal wing disc which, in the absence of interaction, yields only proximal wing structures. These results suggest that spatial organization is controlled by similar systems in the various thoracic discs. In contrast, head and genital disc material provided no regenerative stimulus to the mutant wing disc tissue. 相似文献
8.
Mirror-image doublets of Stylonychia mytilus include 2 sets of cortical structures, one with the normal “right-handed” (RH) arrangement, the other with a reversed “left-handed” (LH) arrangement. These sets, however, are incomplete, with certain structures, most notably cirri of the right marginal type, missing near the line of symmetry. When a mirror-image doublet is bisected longitudinally to separate the RH and LH components physically, each fragment undergoes a regeneration process that restores a complete set of cortical structures, including the previously missing cirri of the right marginal type. In the resulting LH cell, all ciliary structures are present in an arrangement that is globally reversed in relation to that found in RH cells; in particular, marginal cirri of the left-marginal type are formed at the cell's right margin, and marginal cirri of the right-marginal type are produced at the cell's left margin. Whereas the regenerated RH fragment always divides and initiates a clone of normal singlets, the LH fragment, though structurally nearly complete, in all cases eventually dies without dividing. The cause of death is starvation due to the formation of an abnormal oral apparatus. In the Discussion, we consider the nature and consequences of a reversal of global positional information. 相似文献
9.
Retinoic acid, local cell-cell interactions, and pattern formation in vertebrate limbs. 总被引:1,自引:0,他引:1
Retinoic acid (RA), a derivative of vitamin A, has remarkable effects on developing and regenerating limbs. These effects include teratogenesis, arising from RA's ability to inhibit growth and pattern formation. They also include pattern duplication, arising as a result of the stimulation of additional growth and pattern formation. In this review we present evidence that the diverse effects of RA are consistent with a singular, underlying explanation. We propose that in all cases exogenously applied RA causes the positional information of pattern formation-competent cells to be reset to a value that is posterior-ventral-proximal with respect to the limb. The diversity of outcomes can be seen as a product of the mode of application of exogenous RA (global versus local) coupled with the unifying concept that growth and pattern formation in both limb development and limb regeneration are controlled by local cell-cell interactions, as formulated in the polar coordinate model. We explore the possibility that the major role of endogenous RA in limb development is in the establishment of the limb field rather than as a diffusible morphogen that specifies graded positional information across the limb as previously proposed. Finally, we interpret the results of the recent finding that RA can turn tail regenerates into limbs, as evidence that intercalary interactions may also be involved in the formation of the primary body axis. 相似文献
10.
P N Adler 《Developmental biology》1979,70(1):262-267
When fragments of the imaginal wing disc from opposite ends of the disc are mixed prior to culture, intercalary regeneration occurs so that structures are produced which neither of the fragments would have produced if they had been cultured alone. I report here that fragments of the imaginal wing and haltere disc interact in a position-specific way. Mixing of homologous fragments does not result in regeneration, while mixing of fragments from opposite ends of the discs does. Thus the interaction of wing and haltere disc fragments shows the same positional specificity as the mixing of two wing fragments. 相似文献
11.
Nodal signals belong to the TGF-β superfamily and are essential for the induction of mesoderm and endoderm and the determination of the left–right axis. Nodal signals can act as morphogens—they have concentration-dependent effects and can act at a distance from their source of production. Nodal and its feedback inhibitor Lefty form an activator/inhibitor pair that behaves similarly to postulated reaction–diffusion models of tissue patterning. Nodal morphogen activity is also regulated by microRNAs, convertases, TGF-β signals, coreceptors, and trafficking factors. This article describes how Nodal morphogens pattern embryonic fields and discusses how Nodal morphogen signaling is modulated.In his 1901 book “Regeneration,” Thomas Hunt Morgan speculated that “if we suppose the materials or structures that are characteristic of the vegetative half are gradually distributed from the vegetative to the animal half in decreasing amounts, then any piece of the egg will contain more of these things at one pole than the other” and “gastrulation depends on the relative amounts of the materials in the different parts of the blastula” (Morgan 1901). Although Morgan’s speculations referred to the sea urchin embryo, they foretold our current understanding of morphogen gradients in frog and fish development. Morgan’s “materials,” “structures,” and “things” are the Nodal signals that create a vegetal-to-animal activity gradient to regulate germ layer formation and patterning. This article discusses how Nodal signaling provides positional information to fields of cells. I first portray the components of the signaling pathway and describe the role of Nodal signals in mesendoderm induction and left–right axis specification. I then discuss how Nodal morphogen gradients are thought to be generated, modulated, and interpreted. 相似文献
12.
Roseland & Schneiderman's (1979) observations on the presence of the intersegmental region anterior to the posterior duplications in the tergite of Drosophila, led them to postulate intercalary regeneration by shortest route to account for pattern duplications. Our observations on the absence of the intersegmental region in these posterior duplications, on the other hand, suggest that pattern duplication in Drosophila abdomen could be explained on the basis of a diffusion morphogen model. Based on the interpretations of the results of grafting experiments in Calliphora (Pearson, 1977) and cauterization studies in Drosophila (Roseland & Schneiderman, 1979), we suggest that the larval epidermal cells located between the dorsal histoblast nests could be the source of this morphogen. During normal development, this morphogen appears to be responsible for the posterior orientation of the cuticular outgrowths in the posterior half of the tergite and the differentiation of the macrochaetae, pigment band and posterior hairy region. Thus, the posteriorizing effects of the morphogen resemble those of the zone of polarizing activity (ZPA) of the developing appendages of the vertebrate embryos. 相似文献
13.
Contribution of cholinesterase to developmental decreases in the time course of synaptic potentials at an amphibian neuromuscular junction 总被引:1,自引:0,他引:1
Urodele limbs are able to regulate for intercalary deletions created when distal regeneration blastemas are grafted to a more proximal level. Using several morphological markers, pigmentation differences between white and dark axolotls, and the difference in nucleolar number between diploid and triploid animals, we show that the entire intercalary regenerate is derived from the stump when wrist or tarsus blastemas are grafted to the midstylopodium of the fore- or hindlimb. The transplanted prospective autopodium forms no more than would be expected in situ. Thus, the rule of distal transformation is not violated during intercalary regeneration in salamanders. The advantages and disadvantages of the several marking techniques are discussed. 相似文献
14.
Morphology and development of left-handed singlets derived from mirror-image doublets of Stylonychia mytilus 总被引:1,自引:0,他引:1
Mirror-image doublets of Stylonychia mytilus include 2 sets of cortical structures, one with the normal "right-handed" (RH) arrangement, the other with a reversed "left-handed" (LH) arrangement. These sets, however, are incomplete, with certain structures, most notably cirri of the right marginal type, missing near the line of symmetry. When a mirror-image doublet is bisected longitudinally to separate the RH and LH components physically, each fragment undergoes a regeneration process that restores a complete set of cortical structures, including the previously missing cirri of the right marginal type. In the resulting LH cell, all ciliary structures are present in an arrangement that is globally reversed in relation to that found in RH cells; in particular, marginal cirri of the left-marginal type are formed at the cell's right margin, and marginal cirri of the right-marginal type are produced at the cell's left margin. Whereas the regenerated RH fragment always divides and initiates a clone of normal singlets, the LH fragment, though structurally nearly complete, in all cases eventually dies without dividing. The cause of death is starvation due to the formation of an abnormal oral apparatus. In the Discussion, we consider the nature and consequences of a reversal of global positional information. 相似文献
15.
S Strub 《Developmental biology》1979,69(1):31-45
Fragments from prospective distal regions of Drosophila male foreleg imaginal discs failed to undergo proximal intercalary regeneration across leg segment borders when mechanically intermixed and cultured for 8 days with various fragments from prospective proximal disc regions. The failure of the distal cells to regenerate proximal leg segments was not due to a general restriction in their developmental potentials: Distal fragments, when deprived of their distal-most tips, regenerated in the distal direction at a high frequency. It is concluded that there exist in Drosophila leg discs the same restrictions with respect to regeneration along the proximodistal leg axis as had been previously observed in legs of several hemimetabolous insect species: Intersegmental discontinuities between grafted tissue pieces are not eliminated by intercalation. Based on the available evidence in hemimetabolous insects and in Drosophila, a new interpretation of the different aspects of regeneration in insect legs is offered. It is proposed that the two categories of regulative fields observed in insect legs, the leg segment fields and the whole leg field, represent the units of regulation for two fundamentally different regulative pathways that a cell at a wound edge can follow, the intercalative pathway and the terminal pathway, respectively. It is suggested that the criterion used by cells at healing wounds to choose between the two pathways is the difference in circumferential positional information between juxtaposed cells. The intercalative regulative pathway is switched on when cells with disparities in their axial positional information, or cells with less than maximal disparities in their circumferential information, contact one another. The terminal regulative pathway is triggered whenever cells with maximal circumferential disparities come into contact. 相似文献
16.
Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi) leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi) animals. We find that the ectopic anterior structures induced by abrogation of Wnt signaling also require Smed-prep to form. We use double knockdown experiments with the S. mediterranea ortholog of nou-darake (that when knocked down induces ectopic brain formation) to show that Smed-prep defines an anterior fated compartment within which stem cells are permitted to assume brain fate, but is not required directly for this differentiation process. Smed-prep is the first gene clearly implicated as being necessary for promoting anterior fate and the first homeobox gene implicated in establishing positional identity during regeneration. Together our results suggest that Smed-prep is required in stem cell progeny as they form the anterior regenerative blastema and is required for specifying anterior cell fates and correct patterning. 相似文献
17.
Regulative feedback in pattern formation: towards a general relativistic theory of positional information 总被引:3,自引:0,他引:3
Positional specification by morphogen gradients is traditionally viewed as a two-step process. A gradient is formed and then interpreted, providing a spatial metric independent of the target tissue, similar to the concept of space in classical mechanics. However, the formation and interpretation of gradients are coupled, dynamic processes. We introduce a conceptual framework for positional specification in which cellular activity feeds back on positional information encoded by gradients, analogous to the feedback between mass-energy distribution and the geometry of space-time in Einstein's general theory of relativity. We discuss how such general relativistic positional information (GRPI) can guide systems-level approaches to pattern formation. 相似文献
18.
V French 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1981,295(1078):601-617
Insect legs develop from small regions of the embryonic thorax. In most insects they differentiate in the embryo, forming functional larval legs, which grow and moult through larval life. In Drosophila the presumptive legs invaginate to form imaginal discs, which grow through larval life but only differentiate in the pupal stage. Analysis of the structures formed after amputation, grafting and wounding experiments on larval legs and on mature and immature imaginal discs suggests that the same organization of positional information and cellular behaviour is involved in the response of tahe developing leg to disturbance at early stages (termed 'regulation') and at later stages (termed 'regeneration'). The results suggest that developing legs form pattern in accordance with positional information specified in two dimensions within the epidermis, along polar coordinates. A continuous sequence of positional values runs around the circumference and an independent sequence runs down the leg. Two rules govern cellular behaviour after a disturbance. The shortest intercalation rule: interaction between cells with different positional values provokes local growth, producing cells with intermediate values (by the shortest route in the case of the circumferential values). The distalization rule: if intercalated cells have positional values identical to those of adjacent pre-existing cells then the new cells adopt a more distal value. These rules will produce a complete distal regenerate from a complete circumference and may produce a symmetrical regenerate from a symmetrical wound surface. This regenerate may taper (converge) or widen (diverge) and branch into two distal tips, depending on the extent of the original wound and the way in which it heals. The polar coordinate model provides a simple and unified interpretation, in terms of only local interactions, of a wide range of experimentally produced and naturally occurring insect (and crustacean and amphibian) limbs showing regeneration of missing structures, duplication of structures, and the formation of complete, tapering or branching supernumeraries. It is not yet clear what molecular mechanisms could underlie a polar map of positional information, nor how such a map could be initially established at a particular site in the early embryo. 相似文献
19.
Jonathan B.L. Bard 《Journal of theoretical biology》1982,94(3):689-708
A model is presented that can, in principle, generate new sources and sinks within an existing gradient in the concentration of a morphogen. The novel and crucial feature of the model is that morphogens are transported between cells by membrane-based carrier molecules and not by diffusion. A further aspect of the model is the presence of a second substance within each cell whose concentration is uniform over the tissue; this molecule binds to but is not transported by the carrier and is therefore a competitive inhibitor of the morphogen. The concentration of free inhibitor in a cell determines its fate: if at any time it exceeds some threshold, that cell becomes a morphogen source; if it falls below a second threshold, the cell becomes a sink; in between them, the cell shows no special properties. Provided that differences in morphogen concentration between adjacent cells are not too great, the mechanism is indistinguishable from a normal, diffusion gradient. Examination of the kinetics of the system over a one-dimensional line of cells, however, shows that any stable morphogen difference leads to a carrier imbalance and to a change in the degree of inhibitor binding. If this difference is sufficiently great and if there is morphogen homostasis in each cell, then the free inhibitor concentration in the high morphogen cell may exceed the higher threshold causing it to become a source while the low morphogen cell becomes a sink.A numerical example of the mechanism is given and the results calculated for two-dimensional cellular arrays on either side of a morphogen discontinuity. The predictions match the observations of Wright & Lawrence (1981a, b) on Oncopeltus. These authors showed that, if pieces of epidermis from sufficiently different positions were grafted together in vivo, an ectopic boundary would form with regions of reversed polarity on either side of the join. The ability of the model to explain the regeneration and axial graft observations on hydra is also discussed and some experiments that might test the model are put forward. It is suggested that the significance of the membrane-carrier mechanism in vivo is twofold: first, to interpret the basic segmentation mechanism in embryogenesis by turning its morphogen discontinuities into source-sink pairs and so generating actual boundaries; second, to act as a homeostatic mechanism in later development, thus ensuring the maintenance of boundaries. 相似文献
20.
A fate map of the female genital disc of Drosophila melanogaster was established by examining the derivatives of fragments transplanted into host larvae for metamorphosis. The fate map is presented as a two-dimensional projection, but for several reasons it is proposed that the anal plates originate from the dorsal epithelial layer whereas the genitalia are produced from the ventral layer. Fragments produced by cuts parallel to the axis of symmetry of the disc undergo regeneration during culture in adult hosts if the fragments comprise more than half of the disc, or duplication if they comprise less than half. Most of the fragments generated by bilaterally symmetrical cuts across the line of symmetry of the disc undergo neither regeneration nor duplication during culture, but with some such fragments there is a low frequency of regeneration. It is argued that the usual lack of regeneration in these fragments results from wound healing which confronts identical positions from right and left sides, giving no growth stimulation. The fragments which regenerate might do so as a result of healing between dorsal and ventral surfaces, providing the discontinuity in positional information which is thought to be involved in growth stimulation. 相似文献