DEVELOPING INNER-EAR SENSORY NEURONS REQUIRE TRKB AND TRKC RECEPTORS FOR INNERVATION OF THEIR PERIPHERAL TARGETS

The trkB and trkC genes are expressed during the formation of the vest ibular and auditory system. To elucidate the function of trkB and trkC during this process, we have analysed mice carrying a germline mutati on in the tyrosine kinase catalytic domain of these genes. Neuroanatom ical analysis of homozygous mutant mice revealed neuronal deficiencies in the vestibular and cochlear ganglia. In trkB (-/-) animals vestibu lar neurons and a subset of cochlear neurons responsible for the inner vation of outer hair cells were drastically reduced. The peripheral ta rgets of the respective neurons showed severe innervation defects. A c omparative analysis of ganglia from trkC (-/-) mutants revealed a mode rate reduction of vestibular neurons and a specific loss of cochlear n eurons innervating inner hair cells. No nerve fibres were detected in the sensory epithelium containing inner hair cells. A developmental st udy of trkB (-/-) and trkC (-/-) mice showed that some vestibular and cochlear fibres initially reached their peripheral targets but failed to maintain innervation and degenerated. TrkB and TrkC receptors are t herefore required for the survival of specific neuronal populations an d the maintenance of target innervation in the peripheral sensory syst em of the inner ear.