NEUROTROPHIN-3 AFFECTS PROLIFERATION AND DIFFERENTIATION OF DISTINCT NEURAL CREST CELLS AND IS PRESENT IN THE EARLY NEURAL-TUBE OF AVIAN EMBRYOS

Neurotrophin-3 is mitogenic for cultured quail neural crest cells (Kal cheim et al., 1992, Proc. Natl. Acad. Sci. USA 89:1661-1665). We now r eport that neurotrophin-3 also influences the survival and/or differen tiation of a subset of postmitotic neural crest precursors into neuron s, provided these progenitors are grown on a cellular substrate. When cultured for 1 day on monolayers of NT-3-producing, chinese hamster ov ary cells, 59% of the neural crest clusters growing on the transfected line revealed the presence of intense neuronal outgrowth, compared to 25% of that in controls. Moreover, dissociated neural crest cells gro wn for 20 h on top of mesodermal cells in the presence of various conc entrations of purified recombinant neurotrophin-3 displayed a dose-dep endent increase in neuronal number. Localization experiments using spe cific polyclonal antibodies, revealed that neurotrophin-3 is confined to neuroepithelial cells of quail neural tubes in situ on E2 and E3, a nd the E2 neural tubes grown in culture for 24 h. At this stage, neura l crest cells and somites were negative. At later stages, staining was likewise apparent in peripheral nerves and dorsal root ganglia. We, t herefore, propose that NT-3, a factor that is expressed in the early a vian central nervous system, has multiple effects both on the prolifer ation and differentiation of distinct neural crest cells, which depend on the state of committent of the responsive progenitors. (C) 1993 Jo hn Wiley & Sons, Inc.