Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targets

TLDR

The trkB and trkC genes are expressed during the formation of the vestibular and auditory system. The study examined mice with germline mutations in the tyrosine kinase catalytic domains of trkB and trkC to elucidate their roles during vestibular and auditory system development. Homozygous trkB and trkC mutant mice show severe deficits in vestibular and cochlear ganglia; trkB loss drastically reduces vestibular neurons and outer‑hair‑cell‑innervating cochlear neurons, while trkC loss moderately reduces vestibular neurons and eliminates inner‑hair‑cell‑innervating cochlear neurons, and in both mutants peripheral innervation initially occurs but then degenerates, indicating that TrkB and TrkC are essential for neuronal survival and maintenance of inner‑ear target innervation.

Abstract

ABSTRACT The trkB and trkC genes are expressed during the formation of the vestibular and auditory system. To elucidate the function of trkB and trkC during this process, we have analysed mice carrying a germline mutation in the tyrosine kinase catalytic domain of these genes. Neu- roanatomical analysis of homozygous mutant mice revealed neuronal deficiencies in the vestibular and cochlear ganglia. In trkB (−/−) animals vestibular neurons and a subset of cochlear neurons responsible for the inner- vation of outer hair cells were drastically reduced. The peripheral targets of the respective neurons showed severe innervation defects. A comparative analysis of ganglia from trkC (−/−) mutants revealed a moderate reduction of vestibular neurons and a specific loss of cochlear neurons innervating inner hair cells. No nerve fibres were detected in the sensory epithelium containing inner hair cells. A developmental study 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 therefore required for the survival of specific neuronal populations and the maintenance of target innervation in the peripheral sensory system of the inner ear.