The inheritance of cell differentiation during limb regeneration in the axolotl

Namenwirth, Marion

doi:10.1016/0012-1606(74)90281-4

Cited by 111 publications

(60 citation statements)

References 11 publications

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“…Blastema cells derived from fibroblasts differentiate into fibroblasts, but have more flexibility in being able to transdifferentiate into chondrocytes and tendon cells. In fact, a complete skeleton can regenerate distal to the plane of amputation from dermal fibroblasts of the skin, as first shown in experiments amputating boneless limbs of newts (Bischler & Guyenot, 1925; Weiss, 1925) and later by Namenwirth (1974) in experiments grafting normal skin in place of the skin of irradiated axolotl limbs.…”

Section: Formation Of the Accumulation Blastemamentioning

confidence: 88%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

109

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This review explores the historical and current state of our knowledge about urodele limb regeneration. Topics discussed are (1) blastema formation by the proteolytic histolysis of limb tissues to release resident stem cells and mononucleate cells that undergo dedifferentiation, cell cycle entry and accumulation under the apical epidermal cap. (2) The origin, phenotypic memory, and positional memory of blastema cells. (3) The role played by macrophages in the early events of regeneration. (4) The role of neural and AEC factors and interaction between blastema cells in mitosis and distalization. (5) Models of pattern formation based on the results of axial reversal experiments, experiments on the regeneration of half and double half limbs, and experiments using retinoic acid to alter positional identity of blastema cells. (6) Possible mechanisms of distalization during normal and intercalary regeneration. (7) Is pattern formation is a self‐organizing property of the blastema or dictated by chemical signals from adjacent tissues? (8) What is the future for regenerating a human limb?

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Section: Formation Of the Accumulation Blastemamentioning

confidence: 88%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

109

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“…Blastemal mesenchyme cells are undifferentiated proliferating cells, which can differentiate into the cartilage, connective tissue, and muscle of a regenerate (Tsonis, 1996). AEC is derived from the stump epidermis and differentiates into the epidermis of the regenerate (Namenwirth, 1974).…”

Section: Introductionmentioning

confidence: 99%

Intercalary and supernumerary regeneration in the limbs of the frog, Xenopus laevis

Shimizu‐Nishikawa¹,

Takahashi²,

Nishikawa³

2003

Developmental Dynamics

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Anuran amphibians, such as Xenopus laevis, can regenerate their limbs only when they are young tadpoles, whereas urodele amphibians have a regenerative ability throughout their lives. It is still unclear whether anuran and urodele use the same mechanism during regeneration. In the present study, we analyzed intercalary and supernumerary regeneration in Xenopus. In contrast to urodele blastema that induces intercalary regeneration along the proximodistal (PD) axis, intercalation did not occur in the Xenopus limb bud when the presumptive zeugopodium (fibula and tibia) was removed. However, when the limb bud tip (presumptive autopodium) was transplanted to the presumptive stylopodium (femur) with a 180-degree rotation at stage 52, the complete zeugopodium was regenerated. These results were similar to the results of urodele mature limbs, suggesting that Xenopus limb buds are equivalent to the urodele mature limbs but not to the urodele blastemas. We hypothesized that the ability for intercalation depends on the expression pattern of fibroblast growth factor (fgf)-8, because the expression of fgf-8 in the urodele spreads over the whole blastema and is close enough to activate the growth of the stump. To test this hypothesis, an FGF-8 -soaked bead was implanted at the boundary between the stump and tip of a Xenopus limb bud. Intercalary regeneration was induced at stages 52 and 53. These results suggest that the Xenopus limb bud possesses the potential for intercalation, but endogenous FGF-8 in the apical ectodermal ridge (AER) does not induce intercalation to the stump because of the long distance between the AER and stump.

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“…Alternately, blastema cells could be multipotent, capable of transdifferentiation into all cell types of the regenerate. Indeed, transdifferentiation has been described in both axolotl tail regeneration (6) and amphibian limb regeneration experiments in which certain tissues were removed or irradiated (7,8). However, recent lineage analyses after amputation of both the axolotl limb and the zebrafish fin strongly suggest that transdifferentiation does not significantly contribute to the regenerates, and that instead the blastemas are made up of lineage-restricted cell populations (9)(10)(11).…”

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confidence: 99%

Mouse digit tip regeneration is mediated by fate-restricted progenitor cells

Lehoczky

Robert²,

Tabin³

2011

Proc. Natl. Acad. Sci. U.S.A.

190

241

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Regeneration of appendages is frequent among invertebrates as well as some vertebrates. However, in mammals this has been largely relegated to digit tip regeneration, as found in mice and humans. The regenerated structures are formed from a mound of undifferentiated cells called a blastema, found just below the site of amputation. The blastema ultimately gives rise to all of the tissues in the regenerate, excluding the epidermis, and has classically been thought of as a homogenous pool of pluripotent stem cells derived by dedifferentiation of stump tissue, although this has never been directly tested in the context of mammalian digit tip regeneration. Successful digit tip regeneration requires that the level of amputation be within the nail bed and depends on expression of Msx1. Because Msx1 is strongly expressed in the nail bed mesenchyme, it has been proposed that the Msx1-expressing cells represent a pluripotent cell population for the regenerating digit. In this report, we show that Msx1 is dynamically expressed during digit tip regeneration, and it does not mark a pluripotent stem cell population. Moreover, we show that both the ectoderm and mesoderm contain fate-restricted progenitor populations that work in concert to regenerate their own lineages within the digit tip, supporting the hypothesis that the blastema is a heterogeneous pool of progenitor cells.

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The inheritance of cell differentiation during limb regeneration in the axolotl

Cited by 111 publications

References 11 publications

Mechanisms of urodele limb regeneration

Mechanisms of urodele limb regeneration

Intercalary and supernumerary regeneration in the limbs of the frog, Xenopus laevis

Mouse digit tip regeneration is mediated by fate-restricted progenitor cells

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