Directed regrowth of axons from a misrouted nerve to their correct muscles in the limb of the adult newt

Abstract

When the forearm flexor nerve (f.f.n.) of the newt forelimb is surgically rerouted to the ventral body wall, regrowth of axons occurs and these axons reinnervate the muscle targets of the f.f.n. This process of nerve regeneration has been studied in detail over a 12 week period by using light and electron microscopy, electrophysiology and nerve fibre tracking after filling with cobalt chloride. The regrowing axons were analysed by electron microscopy and it is shown that they derive from the rerouted nerve at the position at which the f.f.n. leaves its normal ventral limb pathway. Axons in the pathway do not originate from the cut end of the f.f.n. on the ventral body wall. The regrowing axons are identified within the body of the rerouted nerve and they leave the f.f.n. by growing through the perineurium. Schwann cells are invariably associated with the regrowing axons and the pathway through which the growth cones and neurites grow consists predominantly of extracellular matrix fibrils. The stages of maturation of the regenerated f.f.n. including fasiculation of neurites, myelination and reformation of a perineurium are also described. The results of the study are discussed in terms of current ideas as to how specific regeneration of a correct and functional peripheral nervous system is achieved in urodele amphibians.

Guidance of regenerating motor axons in larval and juvenile bullfrogs

“…In fact, regenerating axons have been reported growing outside Schwann tubes and through tube walls (Ramon y Cajal, 1928;Bennett et al, 1973;Holder et al, 1984;Krarup and Gilliatt, 1985). It remains possible that regenerating axons exhibit a preference for growth along particular structures within the distal stump but are not rigidly confined by them.…”

Regeneration of specific innervation inXenopus pectoralis muscle

“…In lower vertebrates, much of this specificity is restored during regeneration following nerve crush or section. Not only is the appropriate muscle reinnervated, but this is the case even when the nerve is forced to take an abnormal pathway or the target muscle is displaced (Grimm, 197 1 ;Stephenson, 1979;Holder et al, 1982Holder et al, , 1984Wigston, 1986;Wigston and Kennedy, 1987). Within the muscle, regenerating nerves reinnervate old end plate sites (Letinsky et al, 1976) and probably selectively reinnervate their original muscle fiber types (Bewick et al, 1993).…”

A study of factors influencing synapse formation by a foreign nerve in skeletal muscle of Rana pipiens.

“…In the mammal regenerating axons reinnervate skeletal muscle in an apparently random manner (Sperry, 1941;Bernstein & Guth, 1961) while in the urodele axons appear able to reinnervate their appropriate target tissues selectively (Grimm, 1971;Cass, Sutton & Mark, 1973;Cass & Mark, 1975;Genat & Mark, 1977;Holder, Tonge & Jesani, 1984). In adult anurans, regenerating motor axons innervate skeletal muscle non-selectively (Hoh, 1971) but the synapses formed by inappropriate axons in a particular muscle release less acetylcholine per nerve impulse (as estimated from the mean quantal content of end-plate potentials) than those formed by the appropriate nerve (Sayers & Tonge, 1982).…”