Neural Control of Cell Cycle Events in Regenerating Salamander Limbs

Nerves, wound epidermis, and injury are indispensable for salamander limb 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 dedifferentiation and entry of limb stump cells into the cell cycle, nerves are required for one or more G2 events in order that cells can proceed to mitosis, and the wound epidermis maintains the daughter cells in the cell cycle. The resultant cells accumulate to form the blastema. Complete and partial denervation experiments, which attempted to test this hypothesis, are discussed. Blastema cell cycle parameters, measured after complete denervation, did not vary greatly from innervated controls, even though denervated blastemas were resorbed. Blastema cell cycle parameters of partially denervated limbs, which exhibited delayed regeneration, were likewise not lengthened when compared to completely innervated controls. These results are consistent with the view that after either complete or partial denervation, some blastema cells continue to cycle and reach the M phase in the same time as controls. Other blastema cells block completely, never reach M, and are then removed. A possible mechanism for resorption of denervated blastemas is presented.