A Reciprocal Cell–Cell Interaction Mediated by NT-3 and Neuregulins Controls the Early Survival and Development of Sympathetic Neuroblasts
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.
© 1996 Cell Press. Under an Elsevier user license. Received December 6, 1995; Revised December 12, 1995. Correspondence should be addressed to D. J. A. We thank George Yancopoulos and Regeneron, Incorporated for their gifts of NT-3 and CNTF; Amgen, Incorporated for NGF, FGF, NT-3, IGF, CNTF, and the gift of anti-NT-3 neutralizing antibody; and David Kaplan for his gift of rabbit anti-NT-3 antibody. We thank Rochelle Diamond for help with cell sorting, Denis Bouchard for technical assistance, and Nirao Shah for advice and helpful discussion. We also thank Pat White for assistance with dissections at early stages in this project. This work was supported in part by a grant from the National Institutes of Health. J. M. V. is an Assistant Investigator of the Amgen Institute. D. J. A. is an Associate Investigator of the Howard Hughes Medical Institute. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked "advertisement" in accordance with 18 USC Section 1734 solely to indicate this fact.
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