ABSENCE OF SENSORY NEURONS BEFORE TARGET INNERVATION IN BRAIN-DERIVEDNEUROTROPHIC FACTOR-DEFICIENT, NEUROTROPHIN 3-DEFICIENT, AND TRKC-DEFICIENT EMBRYONIC MICE

Gene-targeting experiments of Trk receptors and neurotrophins has conf irmed the expectation that embryonic sensory and sympathetic neurons r equire neurotrophin function for survival. They have further revealed correlation between a specific neurotrophin requirement and eventual s ensory modality. We have analyzed embryonic and neonatal mice with mut ations in the BDNF, neurotrophin 3 (NT-3), and TrkC genes. Our data co nfirm an unexpectedly high proportion of sensory neuron losses in NT-3 (>70%), BDNF (>20%), and TrkC (>30%) mutants, which encompass populat ions thought to be NGF-dependent. Direct comparison of TrkC and NT-3 m utants indicates that only a subset of the NT-3-dependent neurons also requires TrkC. The observed losses in our TrkC mutant, which is null for all proteins encoded by the gene, are more severe than those previ ously reported for the kinase-negative TrkC mutation, implicating addi tional and important functions for the truncated receptors. Our data f urther indicate that mature NGF-requiring neurons undergo precocious a nd transitory requirements for NT-3 and/or BDNF. We suggest that neuro trophins may function in creating early heterogeneity that would enabl e ganglia to compensate for diverse modality requirements before the p eriod of naturally occurring death.