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Volume 16, Number 11, Issue of June 1, 1996 pp. 3704-3713
Copyright ©1996 Society for Neuroscience

Inhibition of the NT-3 Receptor TrkC, Early in Chick Embryogenesis, Results in Severe Reductions in Multiple Neuronal Subpopulations in the Dorsal Root Ganglia

Received Dec. 6, 1995; revised March 5, 1996; accepted March 7, 1996.

Frances Lefcort^{1, 2}, Douglas O. Clary^{1, 3}, Anne C. Rusoff², and Louis F. Reichardt¹

¹ Howard Hughes Medical Institute and Department of Physiology, University of California, San Francisco, San Francisco, California 94143-0724, ² Department of Biology and WAMI Medical Program, Montana State University, Bozeman, Montana 59717, and ³ Sugen Incorporated, Redwood City, California 94063

To assess functions of neurotrophins at defined times in development, we have prepared antibodies to the extracellular domains of each of the trk receptors. Here, antibodies to trkC, the major receptor for NT-3, are used to examine trkC expression and function during the formation and maturation of the chick dorsal root ganglion (DRG). Our results show that in the immature DRG, the majority of cells express trkC, and inhibition of trkC activation results in reductions in neuronal numbers before the period of target-mediated cell death, the time when neurotrophins previously have been shown to regulate survival. Furthermore, blockade of trkC in ovo induced reductions in subpopulations of DRG neurons known to be dependent on NGF, in addition to those dependent on NT-3 during the target-regulated cell death period. An early function for NT-3 on immature DRG neurons is supported further by data presented here that demonstrate that whereas BDNF and NGF can support a subset of immature DRG neurons in vitro, activation of the trkC receptor either by NT-3 binding or via antibody-mediated cross-linking induces the most robust survival response. When all three neurotrophins are combined, the number of surviving neurons does not exceed that supported by NT-3 alone. Together, these data are consistent with coexpression of more than one trk receptor family member on immature sensory neurons, and they demonstrate that inhibition of trkC activation has surprisingly early and pleiotrophic effects on the development of spinal sensory ganglia.

Key words: trkC receptor; neurotrophin-3; DRG; chicken; differentiation; antibody blockade

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