Radioresistance of nerves in amphibian limb regeneration

Abstract

The limbs of salamanders can regenerate even if their nerves are irradiated, provided that some other non-irradiated tissue reaches the site of amputation. This conclusion is reached by repetition of an earlier experiment, which yielded contradictory results. The experimental design does not demonstrate any radiosensitivity of nerves, but indicates that very few non-irradiated cells suffice to initiate regeneration. On the basis of this conclusion and other unconfirmed experiments, the possibility is considered that irradiated cells can recover their ability to regenerate.

Cellular contribution from dermis and cartilage to the regenerating limb blastema in axolotls

“…The dermis of the axolotl is composed of two morphologically distinct cell types, fibroblasts and pigment cells, arranged diffusely in a network of extracellular fibers (Holder and Glade, 1984). Pigment cells can be eliminated as being important for the regeneration process since the limbs of the axolotl mutant d/d, which lack these cells, regenerate perfectly well (see Wallace and Wallace, 1973). Fibroblasts are by far the most abundant cell type in the dermis and are almost certainly responsible for the dermal contribution to the blastema, as well as for the patterning role of the dermis.…”

Novel Insights into the Flexibility of Cell and Positional Identity during Urodele Limb Regeneration

“…Selective Xirradiation of the limb stump before limb amputation demonstrated that the cells for the blastema arise locally from the tissues at the amputation plane (Butler 1931). Tracking of triploid or tritiated thymidine-labeled tissue showed that multiple tissues including dermis, muscle, cartilage, and Schwann cells likely contribute to the blastema and thus the regenerating limb (Steen 1968;Wallace 1973;Namenwirth 1974;Dunis and Namenwirth 1977;Lheureux 1983;Holder 1989).…”

“…Indeed, the term blastema connotes a group of highly plastic progenitors, and it would be fair to say that the general expectation favored pluripotency of at least some blastema cells. For example, Wallace (1973) found that the implantation of healthy nerves into irradiated limbs was sufficient to rescue regeneration, implying that cells of neural origin could generate nonneural tissue. In a more recent study, satellite cells isolated from newt muscle tissue and labeled with bromodeoxyuridine (BrdU) were reimplanted into blastemas and contributed to cartilage and even epidermis of the regenerating limb, suggesting high plasticity of muscle-derived cells (Morrison et al 2006).…”

Cellular plasticity in vertebrate regeneration

“…These regenerates contained not only cartilage, but also muscle, nerve sheaths, blood vessels, and connective tissues, suggesting that the chondrocytes had undergone a metaplastic transformation into these other cell types by progressing through a multipotent progenitor state during the blastema stage of regeneration. These results are compelling evidence for metaplasia, because it has been shown that cells from irradiated limbs do not contribute to the regenerate following implantation of nonirradiated tissues (Wallace, 1972;Wallace and Wallace, 1973). However, pure chondrocytes from older larval specimens have not shown this degree of metaplasia (Steen, 1968;Namenwirth, 1974;Wallace et al, 1974).…”

“…This is strong evidence for metaplasia, given that no bone or cartilage was present near the amputation site and that it has been shown that the regeneration blastema is derived primarily, if not entirely, from local tissues (Butler, 1935;Butler and O'Brien, 1942). Another study showed that when cartilage from young larval axolotls was stripped of its perichondrium and transplanted into irradiated axolotl limbs (irradiated limbs do not regenerate), 70% of the limbs regenerated following amputation and produced deformed limbs consisting of one to four digits (Wallace et al, 1974). These regenerates contained not only cartilage, but also muscle, nerve sheaths, blood vessels, and connective tissues, suggesting that the chondrocytes had undergone a metaplastic transformation into these other cell types by progressing through a multipotent progenitor state during the blastema stage of regeneration.…”