Role of neurotrophins and trk receptors in the development and maintenance of sensory neurons: an overview.

The neurotrophins are a family of polypeptide neuronal growth factors related to the prototypical neurotrophic factor, nerve growth factor (NGF). In mammals this gene family encompasses NGF, brain-derived neurotrophic factor (BDNF) and neurotrophins-3 and -4/5, (NT-3, NT-4/5). The neurotrophins initiate signal transduction in responsive cells by ligand induced dimerization and activation of one of the Trk family of receptor tyrosine kinases; NGF being specific for TrkA, BDNF and NT-4/5 for TrkB, and TrkC the preferred receptor for NT-3. In accord with differential patterns of distribution of Trk receptors in peripheral ganglia, the neurotrophins show both distinct and overlapping specificity towards subpopulations of sensory neurons of both neural crest and neural placode origin. In vitro and in vivo studies, and transgenic mice baring targeted null mutations of the neutrophin genes have established that BDNF, NT-3 and NT-4/5, like NGF, play critical roles as classical target-derived survival factors for subclasses of developing sensory neurons. However, much broader effects of neurotrophins on sensory neurons are now evident, including paracrine and autocrine actions on neuroblast proliferation, phenotypic differentiation, and survival and regeneration in the adult. This article provides an overview of the discovery and properties of the neurotrophin family, their receptors and their actions and specificity for both distinct and overlapping subpopulations of spinal and cranial sensory neurons.