Ciliary neurotrophic factor is required for motoneuron sprouting.

We used mutant mice that lack the gene for ciliary neurotrophic factor (CNTF) to test the hypothesis that it is an endogenous sprouting factor. Fibers in the lateral gastrocnemius muscle were either partially denervated by transection of one of the branches of its nerve or paralyzed by intramuscular injection of botulinum toxin. This results in a significant sprouting response at the terminals of intact motoneurons in normal animals. We did not detect sprouting produced by either stimulus in mice lacking CNTF. When exogenous CNTF was administered to CNTF knockout mice following partial muscle denervation, they mounted a typical sprouting response. Thus CNTF is a critical factor in the process of sprout formation after both partial denervation injury and neuromuscular paralysis. It may function as part of a cellular compensatory mechanism after neuronal injury.