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

Muneoka, Ken; Fox, Warren F.; Bryant, Susan V.

doi:10.1016/0012-1606(86)90062-x

Cited by 176 publications

(188 citation statements)

References 22 publications

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“…Hay (1958) described the dedifferentiation of chondrocytes in the regenerating larval urodele limb, and Onda and Tassava (1991) described the strong expression of an antigen, 9G1, in dedifferentiating newt limb chondrocytes during histolysis and blastema formation. However, triploid‐labeled cartilage gave rise to few chondrocytes in the regenerate when grafted to the diploid axolotl limb (Muneoka, Fox et al., 1986a; Steen, 1968) and chondrocytes were not observed to contribute to the blastema at all in another set of experiments where GFP‐labeled cartilage was injured in evoking the formation of a supernumerary blastema and limb (McCusker, Diaz‐Castillo, Sosnik, & Gardiner, 2016). This issue should be explored further to determine whether the skeletal contribution to the blastema is via the periosteum, cartilage/bone, or both, and whether there may be species and developmental stage related differences in skeletal contribution to the blastema, as for muscle.…”

Section: Formation Of the Accumulation Blastemamentioning

confidence: 99%

“…The wound epidermis itself makes no contribution to this cell population (Riddiford, 1960). Nearly half the cells of the blastema are derived from dermal fibroblasts (Muneoka, Fox, and Bryant, 1986a), but the total fibroblast contribution is probably well above 50% when the fibroblasts of the periosteum, muscle interstitial tissue, and nerve sheath are considered. Experiments in which transgenic green fluorescent protein (GFP) neurula stage axolotl tissues contributing to the limb were grafted in place of their counterparts in non‐GFP neurulae and the developed limbs amputated showed that dermal fibroblasts, Schwann cells, skeletal cells, and myogenic cells contribute to the blastema (Kragl et al., 2009; Fig.…”

Section: Formation Of the Accumulation Blastemamentioning

confidence: 99%

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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: 99%

Section: Formation Of the Accumulation Blastemamentioning

confidence: 99%

Mechanisms of urodele limb regeneration

Stocum

2017

Regeneration

109

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“…The cartilage of the regenerate is thus derived from two sources, chondrocytes and fibroblasts. In fact, triploid-marking experiments have shown that dermal fibroblasts contribute nearly half the blastema cells of the amputated axolotl limb, and contribute the majority of the regenerated chondrocytes (Muneoka et al, 1986a). However, the possibility remained that stem cells also contributed to the regeneration blastema.…”

Section: Origin Of Blastema Cellsmentioning

confidence: 99%

Looking proximally and distally: 100 years of limb regeneration and beyond

Stocum

Cameron

2011

Developmental Dynamics

106

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The experimental study of amphibian limb regeneration spans most of the 20 th century and the first decade of the 21 st century. We first review the major questions investigated over this time span: (1) the origin of regeneration blastema cells, the mechanism of tissue breakdown that liberates cells from their tissue organization to participate in blastema formation, (3) the mechanism of dedifferentiation of these cells, (4) how the blastema grows, (5) how the blastema is patterned to restore the missing limb structures, and (6) why adult anurans, birds and mammals do not have the regenerative powers of urodele salamanders. We then look forward in a perspective to discuss the many unanswered questions raised by investigations of the past century, what new approaches can be taken to answer them, and what the prospects are for translation of basic research on limb regeneration into clinical means to regenerate human appendages. Developmental Dynamics 240:943-968,

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“…11 The progeny of dermal fibroblasts account for between 19 and 78% of the cells of the early blastema (42% on average), even though dermal fibroblasts represent less than 20% of the cells of the stump, suggesting that the fibroblast population is subject to selective expansion in the blastema. Since dermal fibroblasts account for about half of all fibroblasts in the limb, 12 it is possible that essentially all of the early blastemal cells are derived from fibroblasts, even though these cells account for less than half of the cells of the mature limb.…”

Section: Fibroblastsmentioning

confidence: 99%