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 sympa thetic neuroblasts before they become nerve growth factor dependent. W e show that NT-3 is produced in vivo by nonneuronal cells neighboring embryonic sympathetic ganglia. NT-3 mRNA is produced by these nonneuro nal cells in vitro and is up-regulated by platelet-derived growth fact or, ciliary neurotrophic factor, and glial growth factor 2 (a neuregul in). Nonneuronal cell-conditioned medium promotes survival and induces TrkA expression in isolated sympathetic neuroblasts, and this activit y is blocked by anti-NT-3 antibody. Neuroblasts also enhance NT-3 prod uction by nonneuronal cells. Neuroblasts synthesize several forms of n euregulin, and antibodies to neuregulin attenuate the effect of the ne uroblasts on the nonneuronal cells. These data suggest a reciprocal ce ll-cell interaction, in which neuroblast-derived neuregulins promote N T-3 production by neighboring nonneuronal cells, which in turn promote s neuroblast survival and further differentiation.