A Reciprocal Cell–Cell Interaction Mediated by NT-3 and Neuregulins Controls the Early Survival and Development of Sympathetic Neuroblasts

• Published in: Neuron (Cambridge, Mass.) Mass.), 1996-03, Vol.16 (3), p.515-527
• Main Authors: Verdi, J.M, Groves, A.K, Fariñas, I, Jones, K, Marchionni, M.A, Reichardt, L.F, Anderson, D.J
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Cell Differentiation; Cell Survival - drug effects; Cells, Cultured; Mice; Molecular Sequence Data; Nerve Growth Factors - pharmacology; Polymerase Chain Reaction; RNA, Messenger - metabolism; Sympathetic Nervous System - drug effects; Time Factors
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80071-9

Neurotrophin 3 (NT-3) can support the survival of some embryonic sympathetic neuroblasts before they become nerve growth factor dependent. We show that NT-3 is produced in vivo by nonneuronal cells neighboring embryonic sympathetic ganglia. NT-3 mRNA is produced by these nonneuronal cells in vitro and is up-regulated by platelet-derived growth factor, ciliary neurotrophic factor, and glial growth factor 2 (a neuregulin). Nonneuronal cell–conditioned medium promotes survival and induces TrkA expression in isolated sympathetic neuroblasts, and this activity is blocked by anti-NT-3 antibody. Neuroblasts also enhance NT-3 production by nonneuronal cells. Neuroblasts synthesize several forms of neuregulin, and antibodies to neuregulin attenuate the effect of the neuroblasts on the nonneuronal cells. These data suggest a reciprocal cell–cell interaction, in which neuroblast-derived neuregulins promote NT-3 production by neighboring nonneuronal cells, which in turn promotes neuroblast survival and further differentiation.