Timing the commitment to a wound-healing response of denervated limb stumps in the adult newt, Notophthalmus viridescens.

Adult newt limbs that are denervated 1 day after amputation undergo a wound-healing response and, although they become reinnervated, will not regenerate unless reinjured. Experiments were designed to determine when denervated limb stumps of adult newts become committed to a wound-healing response. In Experiment I, limbs were amputated and denervated 1 day after amputation. On days 7, 14, 21, 28, and 35 days after the initial amputation and denervation, stumps were reamputated to remove the distal tip. This design varied the time the distal stump was devoid of nerves before reamputation. None of the limbs reamputated at 7 days regenerated. About half of the limbs reamputated at 14 days regenerated and almost all of those reamputated at days 21, 28, and 35 regenerated. In Experiment II, limbs were denervated and then amputated on day 7 or 14, at two different levels. Limbs with a short stump became innervated earlier and regeneration occurred more frequently at both levels of amputation. The results of these experiments show that denervated limb stumps become committed to a wound-healing response between days 7 and 14 after amputation/denervation. If sufficient nerves arrive before day 7, a regeneration response is initiated. If the stump is denervated for 14 days or longer, commitment to wound healing occurs and ingrowing nerves cannot initiate a regeneration response.