▪ REVIEW Axons, Schwann Cells, and Neurotrophic Factors

As most elegantly confirmed by the recent success in deriving mice with null mutations in the genes for specific neurotrophic factors or their respective receptors, it is clear that neurotrophic factors alone or in combination are essential for the development of many classes of neurons. Specific neurotrophic factors have now been characterized that have actions on primary sensory afferents, sympathetic and parasym-pathetic neurons, and motor neurons—the major contributors to the axon bundles that comprise the periph-eral nervous system. The peripheral tissues or "end organs " that these neurons innervate have traditionally been thought of as the key source of neurotrophic factor support, but it is now evident that this "target-derived neurotrophic factor hypothesis " has restricted validity. Rather, the totality of neurotrophic support required to promote the survival, maturation, and maintenance of a neuron appears to be derived not only from targets, but also from support cells and possibly even neurons themselves. In this article, we review the role played by multiple sources of neurotrophic factors, especially factors derived from non-neuronal cells, not only in development, but also in the maintenance and regenerative responses of the adult PNS. In par-ticular, we focus on neurotrophic factors of the neurotrophin family and ciliary neurotrophic factor. The Neuro