ROLE OF NEUROTROPHINS IN MOUSE NEURONAL DEVELOPMENT

During vertebrate development, naturally occurring neuronal cell death is regulated by target-derived peptide factors, called neurotrophins. A recent series of papers describe the phenotypes of germline-targeted mutant mice deficient in neurotrophins and their receptors. Histological analysis of these mice for the first time has provided knowledge about the specific neuron populations that are dependent on neurotrophin action for development. Mice deficient for nerve growth factor (NGF) and its high-affinity receptor, encoded by the trkA proto-oncogene, suffer from complete loss of sympathetic neurons and sensory neurons responsive to temperature and pain. Mice deficient for brain-derived neurotrophic factor (BDNF) and its receptor, encoded by the trkB gene, display loss of sensory neurons responsive to tactile stimuli. In addition, trkB mutant mice experience loss of motor neurons indicating a possible specific function of the second TrkB ligand, neurotrophin-4 (NT-4), in motor neuron development. Mice deficient for neurotrophin-3 (NT-3) and its receptor, encoded by the trkC gene, show abnormal movements caused by the loss of sensory proprioceptive neurons.