Molecular control of neuronal survival in the chick embryo.

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Neurotrophins are structurally related proteins which promote the survival and differentiation of specific neuronal populations during the development of vertebrate embryos. Like many growth factors, the neurotrophins mediate their actions by binding to membrane proteins that have a ligand-activated tyrosine kinase activity. The interactions of the neurophins with their neuronal receptors have been mostly studied using chick embryonic neurons. These neurons are also extensively used to characterise biological responses to neurotrophins in physiologically relevant systems. We have recently cloned and expressed the chick homologue of trkB (ctrkB), thought to be a receptor for BDNF, and examined by in situ hybridisation the pattern of expression of the ctrkB gene during development of the chick embryo. We found that whereas the sequence of ctrkB shows a high degree of conservation with the mammalian homologues in the intracellular tyrosine kinase domain, the extracellular binding domain is less well conserved. As in mammals, ctrkB mRNAs appear to exist in differentially spliced forms that result in a full length and a truncated receptor lacking the tyrosine kinase domain. These two forms are differentially expressed in neurons and non-neuronal cells respectively. The binding characteristics of ctrkB expressed in a transfected cell line are similar, but not identical to those of the BDNF binding sites on primary chick neurons, specially with regard to the affinity of BDNF.