Neural Control of Cell Cycle Events in Regenerating Salamander Limbs

Nerves, wound epidermis, and injury are indispensable for salamanderlimb regeneration, but their mechanism of action is not understood.A hypothesis has been presented (Tassava and Mescher, 1975)which suggests that injury is important to dedifferentiationand entry of limb stump cells into the cell cycle, nerves arerequired for one or more G₂ events in order that cells can proceedto mitosis, and the wound epidermis maintains the daughter cellsin the cell cycle. The resultant cells accumulate to form theblastema. Complete and partial denervation experiments, which attemptedto test this hypothesis, are discussed. Blastema cell cycleparameters, measured after complete denervation, did not varygreatly from innervated controls, even though denervated blastemaswere resorbed. Blastema cell cycle parameters of partially denervatedlimbs, which exhibited delayed regeneration, were likewise notlengthened when compared to completely innervated controls.These results are consistent with the view that after eithercomplete or partial denervation, some blastema cells continueto cycle and reach the M phase in the same time as controls.Other blastema cells block completely, never reach M, and arethen removed. A possible mechanism for resorption of denervatedblastemas is presented.