DEVELOPMENT OF SURVIVAL RESPONSIVENESS TO BRAIN-DERIVED NEUROTROPHIC FACTOR, NEUROTROPHIN-3 AND NEUROTROPHIN-4 5, BUT NOT TO NERVE GROWTH-FACTOR, IN CULTURED MOTONEURONS FROM CHICK-EMBRYO SPINAL-CORD/

During embryonic development, most neuronal populations undergo a proc ess usually referred to as naturally occurring neuronal death. For mot oneurons (MTNs) of the lumbar spinal cord of chick embryos, this proce ss takes place in a well defined period of time, between embryonic day s 6 and 10 (E6-E10). Neurotrophins (NTs) are the best characterized fa mily of neurotrophic factors and exert their effects through activatio n of their specific Trk receptors. In vitro and in vivo studies have d emonstrated that rodent motoneurons survive in response to BDNF NT3, a nd NT4/5. In contrast, the trophic dependencies of chicken motoneurons have been difficult to elucidate, ano various apparently conflicting reports have been published. In the present study, we describe how fre shly isolated motoneurons from E5.5 chick embryos did not respond to a ny neurotrophin in vitro. Yet, because motoneurons were maintained ali ve in culture in the presence of muscle extract, they developed a dela yed specific survival response to BDNF, NT3, and NT4/5 that is clearly dose-dependent, reaching saturation at doses of 100 pg/ml. This troph ic response correlated with increasing expression of the corresponding functional receptors TrkB and TrkC. Moreover, TrkB receptor is able t o become autophosphorylated and to activate classical intracellular si gnaling pathways such as the extracellular signal-regulated protein ki nase when it is stimulated with its cognate ligand BDNF. Therefore, ou r results reconcile the reported differences between in vivo and in vi tro studies on the ability of chicken MTNs to respond to some members of the neurotrophin family of trophic factors.