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Biomedical subjects

M Maden

Publications and source records attributed to M Maden.

At least 109 records · Page 6Linked to original sources
PubMed1980

Intercalary regeneration in the amphibian limb and the rule of distal transformation.

The applicability to the amphibian limb of the rule of distal transformation, which states that tissue from any level can only become more distal, has been tested during intercalary regeneration following various types of shift-level transplantation. Following the grafting of distal blastemas to proximal levels, such that part of the presumptive pattern is missing, complete limbs nevertheless formed (Series I). That the intercalated tissue arose entirely from the stump was shown by exchanging blastemas between black and white animals. When the proximal stump was irradiated and its contribution eliminated, intercalary deletions were produced (Series II). This was not due to the inability of irradiated and normal tissue to communicate since irradiated distal blastemas grafted onto proximal stumps still stimulated intercalary regeneration (Series III). When proximal blastemas were grafted to distal levels intercalary regenerates were obtained in about 20% of the cases (Series IV) and under these circumstances the grafted blastema was the sole source of intercalated tissue. The precise structure of these intercalated elements was impossible to ascertain, but it is suggested that they might be of reversed polarity as found in insects. These results are dicussed in relation to similar experiments on the insect limb.

Ambystoma↗
PubMed1980

Experiments on developing limb buds of the axolotl Ambystoma mexicanum.

Various experiments were performed on the limb buds of axolotls to compare the behaviour of amphibian limbs with that previously reported for chick limbs. Following removal of the tip or whole limb bud, extensive powers of regulation were observed since complete limbs always formed. Similarly after distal to proximal grafts intercalary regulation occurred to produce perfect limbs and after proximal to distal grafts serial repetitions resulted. Transplantation and rotation of limb buds to reverse either the dorso-ventral, antero-posterior or both axes resulted in the induction of supernumerary limbs in a large proportion of cases. Such regulatory behaviour of axolotl limb buds is in contrast to the mosaic nature of chick limbs and as a result, theories such as the progress-zone theory which have been formulated on the basis of data from chick limbs are not relevant to general principles of vertebrate limb development. Possible reasons for the diverse behaviour between the two systems are discussed.

Ambystoma↗
PubMed1979

Neurotrophic and x-ray blocks in the blastemal cell cycle.

Using microdensitometry techniques the points in the cycle where blastemal cells become blocked after X-irradiation or denervation of the regenerating amphibian limb have been identified. X-irradiation blocks the cells in both G1 and G2 and those cells that were in S at the time of irradiation presumably proceed to G2. After denervation, however, cells accumulate only in G1 and those that were in S or G2 continue through the cycle to the next G1. The latter results are clearly contradictory to a recent theory proposing a G2 neurotrophic control of blastemal cells and a solution to the contradiction is presented in the light of recent results.

Ambystoma↗
PubMed1979

The role of irradiated tissue during pattern formation in the regenerating limb.

The amphibian limb regeneration blastema is used here to examine whether irradiated, non-dividing tissue can participate in the development of new pattern of morphogenesis. Irradiated blastemas were rotated 180 degrees on normal stumps and normal blastemas rotated on irradiated stumps. In both cases supernumerary elements developed from the unirradiated tissue. The supernumeraries were defective but this did not seem to be due to a lack of tissue. Rather it suggested that this could be a realization of compartments in vertebrate development or simply reflect the limited regulative ability of the blastema. The results are also discussed in relation to a recent model of pattern formation.

Ambystoma↗
PubMed1979

Regulation and limb regeneration: the effect of partial irradiation.

The regulative ability of the regeneration blastema has been studied by the technique of partial irradiation. Longitudinal halves of fore- and hindlimbs were irradiated and the product of regeneration from the unirradiated halves characterized. Such half irradiated limbs could regulate only to a very limited extent. In the upper arms the anterior halves merely produced a few autopodial elements whereas complete limbs regenerated from the posterior halves. This striking regenerative inequality was less marked in the lower arm where the two halves each produced regenerates of two to three digits. In the hindlimb dorsal halves produced more than ventral halves and thus it was concluded that the posterior-dorsal quadrant has some special regenerative property. These results highlight the inadequacy of current models of limb regeneration and are discussed with reference to the arrangement of positional values in the limb and the question of the totipotency of blastemal cells.

Ambystoma↗
PubMed1978

Neurotrophic control of the cell cycle during amphibian limb regeneration.

It is shown here that amputated and denervated limbs of larval axolotls dedifferentiate and a proportion of the cells released undergo DNA synthesis and mitosis. When the limb is denervated prior to amputation fewer cells go through the cell cycle, implying the existence of a pool of trophic factor in the limb. Recent work has demonstrated that denervated blastemal cells accumulate in the G1 phase of the cycle. These results strongly argue against the theory that the trophic factor controls the G2 phase. Rather, it is proposed that this factor regulated either the total number of cells cycling or the rate at which they cycle by varying the length of the G1 phase.

Ambystoma↗
PubMed1977

The role of Schwann cells in paradoxical regeneration in the axolotl.

The experiments described here examine further the conditions under which paradoxical regeneration occurs and provide support for the hypothesis that a proximal migration of Schwann cells is responsible for the phenomenon. When only the hand is shielded from irradiation and the limb is denervated, amputation through the forearm or upper arm sometimes results in regeneration. The effects of variation in the time interval between denervation and amputation, the level of amputation and the method and number of denervations on the incidence of regeneration were investigated. The presence or absecce of viable Schwann cells at the amputation plane was deduced from the remyelination of nerves under conditions which do or do not permit paradoxical regeneration. The nerves of totally irradiated and denervated limbs remain unmyelinated following regrowth of axons and such limbs do not regenerate after amputation. When only the hand was shielded from irradiation before the limbs were denervated, the new axons became completely remyelinated and some of these limbs regenerated when amputated. It is suggested that under these conditions Schwann cells can migrate proximally and can then proliferate further to form a blastema, since they would be the only unirradiated tissue present at the amputation plane.

Ambystoma↗
PubMed1976

Irradiation inhibits the regeneration of aneurogenic limbs.

The developing arms of axolotl larvae from the 2-digit stage onward and the aneurogenic arms of surgically denervated larvae maintained in parabiosis are able to regenerate after amputation. Such regeneration is uniformly inhibited by local irradiation of the arm, whether innervated or not. This demonstration refutes a recent hypothesis that X-rays interfere with a special activity of nerves required for regeneration, and supports the earlier concept that X-rays act directly on those cells which must proliferate to form the regenerated tissues.

Ambystoma↗
PubMed1976

How x-rays inhibit amphibian limb regeneration.

The effects of an inhibiting dose of 2,000 rad of X-rays on the regenerating limbs of axolotl larvae have been examined in a histological and cytological study. Particular attention was paid to the mitotic indices of normal and irradiated epidermal and blastemal cells. Both the characteristic pattern of epidermal mitotic stimulation which normally follows amputation and the later increase in blastemal mitoses are suppressed by irradiation. In most cells the effects are permanent, but in a small proportion a mitotic delay is induced and upon subsequent division chromosome damage in the form of micronuclei is revealed. Thus irradiated cells which do divide almost certainly die. These results are discussed in relation to other theories of X-ray inhibition of regeneration with particular reference to the view that irradiated cells can be reactivated.

Ambystoma↗
PubMed1976

The cell cycle during amphibian limb regeneration.

The duration of the cell cycle in the blastema of regenerating limbs of axolotls has been measured by means of [3H]thymidine pulse labelling and autoradiography. A chase was required to define the pulse period. An average cell cycle at 20 degrees C takes 53 h, S-phase takes 38 h; including parts of mitosis, G1 is 10 h and G2 is 5 h long. The protracted cycle and S-phase are consonant with the large genome in axolotis and other urodeles. The rapidly growing blastema probably contains a steady population of about 5000 proliferating cells, as there is a regular withdrawal of differentiating cells from the population. The kinds of determination which exist in this population of cells, or are exerted on it, are briefly considered.

Ambystoma↗
PubMed1976

Blastemal kinetics and pattern formation during amphibian limb regeneration.

To investigate whether the uniqueness of proximal and distal limb regenerates could be attributed simply to differing blastemal growth characteristics, their increase in volume, cell number and cell-cycle times were determined. With respect to these parameters proximal and distal blastemas were identical and, furthermore, no evidence could be found for the existance of separate growth zones such as an apical proliferation centre or a progress zone within the blastema. It was therefore concluded that level-specific properties of the blastemal cells play the major role in determining the structure of the regenerate, not their growth characteristics. The only discernible difference was in the cell number within the two types of blastema at the onset of cartilage redifferentiation - proximal regenerates had 60% more cells. Thus it seems that the larger the pattern to be regenerated (the more proximal the amputation plane), the larger the primordium within which that pattern first appears. These two conclusions are discussed in relation to current theories of pattern formation during limb regeneration and development and a few way of envisaging the regeneration of pattern is described.

Ambystoma↗
PubMedDate not supplied

Retinoids as endogenous components of the regenerating limb and tail.

The role of retinoids (vitamin A derivatives) in limb and tail regeneration is the focus of this review. The dramatic effects of excess retinoids on regeneration are considered, which consist of the respecification of each of the cardinal axes of the limb and the transformation of tail regenerates into limbs. The evidence that retinoids are endogenous components of the regeneration blastema and are required for normal regeneration is then addressed. This evidence consists of the fact that various techniques can detect endogenous retinoic acid in the blastema and that retinoic acid receptors are present, and an individual function in regeneration has been established for each of three receptors. Finally, experiments are described in which retinoic synthesis has been inhibited, and this results in the inhibition of both limb development and limb and tail regeneration.

Animals↗
PubMedDate not supplied

The molecular basis of positional information.

Embryologists have dreamed of their own particular philosophers stone for 100 years. During that time they have repeatedly demonstrated the likely existence of signalling molecules or morphogens that control the pattern of development in the embryo. Now at last seems possible that some of these morphogens may have been identified. We review current evidence for the molecular basis of positional information.

Animals↗