The growth influence of spinal ganglia implanted into the denervated forelimb regenerate of the newt, triturus

Kamrin, Anne A.; Singer, Marcus

doi:10.1002/jmor.1051040303

Cited by 33 publications

(8 citation statements)

References 23 publications

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“…Dorsal root ganglia, which are capable of rescuing regeneration if grafted into a denervated limb (Goldhamer et al, 1992;Kamrin and Singer, 1959;Tomlinson and Tassava, 1987), showed extensive NRG1 and ErbB2 staining (Fig. 1M,O).…”

Section: Results and Discussion Nrg1 And Erbb2 Are Expressed In Regenmentioning

confidence: 99%

Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

et al. 2016

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The Mexican axolotl (Ambystoma mexicanum) is capable of fully regenerating amputated limbs, but denervation of the limb inhibits the formation of the post-injury proliferative mass called the blastema. The molecular basis behind this phenomenon remains poorly understood, but previous studies have suggested that nerves support regeneration via the secretion of essential growthpromoting factors. An essential nerve-derived factor must be found in the blastema, capable of rescuing regeneration in denervated limbs, and its inhibition must prevent regeneration. Here, we show that the neuronally secreted protein Neuregulin-1 (NRG1) fulfills all these criteria in the axolotl. Immunohistochemistry and in situ hybridization of NRG1 and its active receptor ErbB2 revealed that they are expressed in regenerating blastemas but lost upon denervation. NRG1 was localized to the wound epithelium prior to blastema formation and was later strongly expressed in proliferating blastemal cells. Supplementation by implantation of NRG1-soaked beads rescued regeneration to digits in denervated limbs, and pharmacological inhibition of NRG1 signaling reduced cell proliferation, blocked blastema formation and induced aberrant collagen deposition in fully innervated limbs. Taken together, our results show that nerve-dependent NRG1/ErbB2 signaling promotes blastemal proliferation in the regenerating limb and may play an essential role in blastema formation, thus providing insight into the longstanding question of why nerves are required for axolotl limb regeneration.

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Section: Results and Discussion Nrg1 And Erbb2 Are Expressed In Regenmentioning

confidence: 99%

Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

et al. 2016

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“…Sensory ganglia were employed as a source of nerve tissue because, while they can sustain limb regeneration of the newt (Kamrin and Singer, 1959), they do not directly innervate the cultured muscle in the time course of these experiments . Thus, any effects on the motor end plate cannot be attributed to normal neuromuscular transmission or direct innervation, but are more likely due to diffusible factors released by the nerve cells .…”

Section: Introductionmentioning

confidence: 99%

Development of the Neuromuscular Junction

Lentz

1972

The Journal of Cell Biology

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To determine the effects of nerve explants on the integrity of motor end plates in vitro, cholinesterase activity and structure of end plates were compared in newt muscle denervated in vivo, cultured in the absence of nerve explants, and cultured in the presence of sensory ganglia . In neuromuscular junctions denervated in vivo or in vitro, the synaptic vesicles become clumped and fragmented . A few intact vesicles escape into the synaptic cleft . Axon terminals degenerate until they are left as residual bodies within the Schwann cell cytoplasm . functional folds on the muscle surface are reduced in height and are no longer evident once traces of axoplasm within the Schwann cell disappear. End plate cholinesterase activity is reduced as junctional folds are lost . When muscle is cultured in the presence of a sensory ganglion, the terminal axoplasm degenerates in the same manner but junctional folds persist on the muscle surface. Moderately intense cholinesterase activity remains in association with the junctional folds, so that normal motor end plates are maintained in the absence of innervation . These results show that degenerative changes in the structure of the motor end plate and loss of cholinesterase activity occurring in organ culture as a result of denervation can be retarded by nerve explants that do not directly innervate the muscle .

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“…Previously, Cannella et al (1998) showed that subcutaneously delivered rhGGF2 alleviated the symptoms of multiple sclerosis in a mouse model for this disease. Implanted DRGs will also "rescue" denervated newt and axolotl blastemas into a regeneration response, particularly if the DRG is implanted at the time of denervation, that is, in a maintenance test as opposed to a restimulation test (Kamrin and Singer, 1959;Tomlinson and Tassava, 1987). Mullen et al (1996) concluded that FGF-2 is the neurotrophic factor of regenerating limbs.…”

Section: Discussionmentioning

confidence: 98%

Cloning and neuronal expression of a type III newt neuregulin and rescue of denervated, nerve-dependent newt limb blastemas by rhGGF2

2000

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The growth influence of spinal ganglia implanted into the denervated forelimb regenerate of the newt, triturus

Cited by 33 publications

References 23 publications

Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration

Development of the Neuromuscular Junction

Cloning and neuronal expression of a type III newt neuregulin and rescue of denervated, nerve-dependent newt limb blastemas by rhGGF2

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