Expression of Trk receptors in the developing mouse trigeminal ganglion: in vivo evidence for NT-3 activation of TrkA and TrkB in addition to TrkC

Animals lacking neurotrophin-3 (NT-3) are born with deficits in almost all sensory ganglia, Among these, the trigeminal ganglion is missing 70% of the normal number of neurons, a deficit which develops during the major period of neurogenesis between embryonic stages (E) 10.5 and E13.5, In order to i dentify the mechanisms for this deficit, we used antisera specific for TrkA , TrkB, and TrkC to characterize and compare the expression patterns of eac h Trk receptor in trigeminal ganglia of wild type and NT-3 mutants between E10.5 and E15.5, Strikingly, TrkA, TrkB, and TrkC proteins appear to be exc lusively associated with neurons, not precursors. While some neurons show l imited co-expression of Trk receptors at E11.5, by E13.5 each neuron expres ses only one Trk receptor. Neuronal birth dating and cell counts show that in wild-type animals all TrkB- and TrkC-expressing neurons are generated be fore E11.5, while the majority of TrkA-expressing neurons are generated bet ween E11.5 and E13.5, In mice lacking NT-3, the initial formation of the ga nglion, as assessed at E10.5, is similar to that in wild-type animals. At E 11.5, however, the number of TrkC-expressing neurons is dramatically reduce d and the number of TrkC-immunopositive apoptotic profiles is markedly elev ated, By E13.5, TrkC-expressing neurons are virtually eliminated. At E11.5, compared to wild type, the number of TrkB-expressing neurons is also reduc ed and the number of TrkB immunoreactive apoptotic profiles is increased, T rkA neurons are also reduced in the NT-3 mutants, but the major deficit dev elops between E12.5 and E13.5 when elevated numbers of TrkA-immunoreactive apoptotic profiles are detected. Normal numbers of TrkA-and TrkB-expressing neurons are seen in a TrkC-deficient mutant, Therefore, our data provide e vidence that NT-3 supports the survival of TrkA-, TrkB- and TrkC-expressing neurons in the trigeminal ganglion by activating directly each of these re ceptors in vivo.