Denervation effects on DNA replication and mitosis during the initiation of limb regeneration in adult newts

Mescher, Anthony L.; Tassava, Roy A.

doi:10.1016/0012-1606(75)90386-3

Cited by 121 publications

(58 citation statements)

References 24 publications

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“…During blastema formation in the axolotl limb dedifferentiated cells and resident stem cells enter the cell cycle, but have a very low mitotic index [143]. High levels of EVI5 might delay the mitosis of blastema cells until the system is certain that all necessary DNA repairs are made prior to mitosis.…”

Section: Resultsmentioning

confidence: 99%

Proteomic analysis of fibroblastema formation in regenerating hind limbs of Xenopus laevis froglets and comparison to axolotl

et al. 2014

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BackgroundTo gain insight into what differences might restrict the capacity for limb regeneration in Xenopus froglets, we used High Performance Liquid Chromatography (HPLC)/double mass spectrometry to characterize protein expression during fibroblastema formation in the amputated froglet hindlimb, and compared the results to those obtained previously for blastema formation in the axolotl limb.ResultsComparison of the Xenopus fibroblastema and axolotl blastema revealed several similarities and significant differences in proteomic profiles. The most significant similarity was the strong parallel down regulation of muscle proteins and enzymes involved in carbohydrate metabolism. Regenerating Xenopus limbs differed significantly from axolotl regenerating limbs in several ways: deficiency in the inositol phosphate/diacylglycerol signaling pathway, down regulation of Wnt signaling, up regulation of extracellular matrix (ECM) proteins and proteins involved in chondrocyte differentiation, lack of expression of a key cell cycle protein, ecotropic viral integration site 5 (EVI5), that blocks mitosis in the axolotl, and the expression of several patterning proteins not seen in the axolotl that may dorsalize the fibroblastema.ConclusionsWe have characterized global protein expression during fibroblastema formation after amputation of the Xenopus froglet hindlimb and identified several differences that lead to signaling deficiency, failure to retard mitosis, premature chondrocyte differentiation, and failure of dorsoventral axial asymmetry. These differences point to possible interventions to improve blastema formation and pattern formation in the froglet limb.

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Section: Resultsmentioning

confidence: 99%

Proteomic analysis of fibroblastema formation in regenerating hind limbs of Xenopus laevis froglets and comparison to axolotl

et al. 2014

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“…The wound epidermis is invaded by sprouting sensory axons within 2-3 days after amputation, while motor axons make intimate contact with mesenchyme cells (presumably prospective muscle) as the blastema forms (Salpeter, 1965;Lentz, 1967). Blastema cells enter the cell cycle and synthesize DNA, but the level of mitosis during blastema formation is very low (Kelly and Tassava, 1973;Tassava et al, 1974;Mescher and Tassava, 1975;Tassava and Mescher, 1975;Tassava and McCullough, 1978;Maden, 1978a;Tassava and Garling, 1979).…”

Section: Blastema Cell Proliferationmentioning

confidence: 99%

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

Stocum

Cameron

2011

Developmental Dynamics

108

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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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“…The cells that are derived from cleavage of the myofi- bers have been shown to synthesize protein actively, suggesting that myofiber fission does not lead to cell necrosis (Bodemer and Everett, 1959). Subsequent studies have confirmed this histological evidence of dedifferentiation and have also shown that following the loss of a limb, many of the cells comprising the internal tissues reenter the cell cycle, progress through mitosis, and migrate distally toward the AEC to form a regeneration blastema (Chalkley, 1954;Hay and Fischman, 1961;Mescher and Tassava, 1975;Gardiner et al, 1986;Muneoka et al, 1986).…”

Section: Cellular Plasticity and Dedifferentiationmentioning

confidence: 84%

Cellular plasticity in vertebrate regeneration

Odelberg

2005

The Anatomical Record Part B

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Within the animal kingdom, there are several examples of organisms with remarkable regenerative abilities. Among vertebrates, newts appear to be the most adept at replacing lost structures and injured organs and can regenerate their limbs, tails, spinal cords, jaws, retinas, lenses, optic nerves, intestines, and heart ventricles. This regenerative ability is dependent on the induction of an unusual degree of cellular plasticity near the site of injury. Mature cells lose their differentiated characteristics and revert to proliferating progenitor cells that will later redifferentiate to replace the lost or injured tissues. This degree of cellular plasticity appears to be restricted to those vertebrates with the most remarkable regenerative abilities and is not observed in mammals. However, in the last several years, there have been a few studies suggesting that certain factors present in newt tissues can induce a dedifferentiation response in mammalian cells. These results suggest that the knowledge gained from studying the molecular basis of cellular plasticity in newts and other regeneration-competent model organisms might one day be used to enhance the regenerative potential in mammals.

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Denervation effects on DNA replication and mitosis during the initiation of limb regeneration in adult newts

Cited by 121 publications

References 24 publications

Proteomic analysis of fibroblastema formation in regenerating hind limbs of Xenopus laevis froglets and comparison to axolotl

Proteomic analysis of fibroblastema formation in regenerating hind limbs of Xenopus laevis froglets and comparison to axolotl

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

Cellular plasticity in vertebrate regeneration

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