Abstract
This chapter discusses various aspects of neurotrophin-3(NT-3) and neurotrophin-4/5(NT-3). NT-3 shows 57 and 58% amino acid identities with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), respectively. Cloning and sequencing the NT-3 gene opened up many possibilities, from design of molecular probes to the generation of mice null mutated for NT-3. NT-3 mRNA was transiently expressed at high levels in the cingulate cortex, during the first 2 weeks after birth, coinciding with the time of innervation by dopaminergic and noradrenergic neurons. NT-3 was expressed at El8 in scattered cells of the medial zone of the developing hippocampus, where granule cells originate. Tyrosine kinase C (trkC) and trkB were also expressed at the same time in the same region. In the brain, NT-4/5 mRNA was widely distributed, with similar levels being highest in pons-medulla, hypo-thalamus, thalamus, and cerebellum. The distribution of NT-4/5 mRNA in peripheral tissues, together with the presence of its high- and low-affinity receptors in peripheral ganglia, suggests a role for this neurotrophin as a target-derived trophic factor for neurons of the peripheral nervous system. NT-4/5 is found to have survival and/or differentiation effects on a wide range of brain neurons.
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