The sequential development of nodal sprouts in mouse muscles in response to nerve degeneration

Nodal sprouting in response to axonal degeneration was studied in silver-stained, wholemount preparations of the thin, sheet-like mouse muscles tensor faciae latae (TFL) and the inferior and superior gluteus maximus. Axon degeneration in TFL and gluteus was produced by cutting the L14 spinal nerve (partial denervation). Axon degeneration in the gluteus was also produced by superior gluteal and TFL nerve section (hemidenervation). Two days after partial or hemidenervation motor nerve nodal sprouts begin to appear in the intramuscular nerves. Sprout growth is rapid, since only a small percentage of sprouts are ever seen not to terminate at endplates. Sprouts continue to appear for at least three weeks after partial denervation, when there are up to five times as many endplates innervated by sprouts as by remaining intact axons. Sprouts arise at nodes near the denervated endplates, which they innervate by growing directly down the degenerating nerve. Sprout initiation proceeds sequentially in partly and hemidenervated muscles, since the average length of sprouts contacting endplates increases with time. Analysis of silver-stained muscles by combined light and electron microscopy shows that this sequential development is unlikely to be a consequence of slow growth and maturation of submicroscopic sprouts initiated nonsequentially throughout the intramuscular nerves. The observations are consistent with a nodal sprouting mechanism which requires a cellular or structural change in the denervated Schwann cell pathway to spread disto-proximally from the terminal ends of the nerves and thereby to permit the growth of nodal sprouts. The initiation of sprout growth may require a diffusible substance from degenerating nerve or denervated muscle.