REGULATION OF NEUROTROPHIN RECEPTOR EXPRESSION DURING EMBRYONIC AND POSTNATAL-DEVELOPMENT

Members of the NGF family of proteins act as neurotrophic agents for d efined populations of peripheral and central neurons during embryonic and postnatal development. We have studied the presence of receptors f or brain-derived neurotrophic factor (BDNF) and neurotrophin-3 and -4/ 5 (NT-3, NT-4/5) by cross-linking radioiodinated neurotrophins to spec ific cell surface receptors. We have identified neurotrophin receptors representing full-length TrkB and TrkC and their truncated forms (lac king a functional cytoplasmic kinase domain) in neuronal as well as in non-neuronal tissues. During chicken embryonic and early postnatal br ain development, expression of full-length TrkB and TrkC proteins prec eded the onset of the truncated forms of these receptors. A similar pa ttern was also observed in mouse embryonic and early postnatal brain. The relative levels of neurotrophin receptors in the basal forebrain a nd in the hippocampus did not change significantly with age in mice. H igh levels of receptors for the three neurotrophins were detected in t he nigrostriatal system. Full-length TrkB and TrkC receptors were foun d in chicken and rat embryonic ventral spinal cord, as well as on puri fied motoneurons. Again, truncated TrkB appeared significantly later t han the full-length form on spinal motoneurons. In chicken embryonic r etina and optic tectum we detected full-length TrkB and TrkC; however, the optic tectum also expressed large amounts of the truncated form o f TrkB. TrkC but not TrkB was detected in chicken embryonic skeletal m uscle, suggesting that NT-3 may have a novel function in this tissue. The presence of neurotrophin receptors in a wide variety of embryonic and postnatal tissues underlines the significant role of BDNF, NT-3, a nd NT-4/5 in embryonic and postnatal development. The regulation of th e ratio of full-length versus truncated neurotrophin receptors may pla y an important role in the development, maturation, and maintenance of various neuronal networks.