Neuronal cell adhesion molecule (NrCAM) is expressed by sensory cells in the cochlea and is necessary for proper cochlear innervation and sensory domain patterning during development

Background: In the cochlea, auditory development depends on precise patterns of innervation by afferent and efferent nerve fibers, as well as a stereotyped arrangement of hair and supporting cells. Neuronal cell adhesion molecule (NrCAM) is a homophilic cell adhesion molecule that controls diverse aspects of nervous system development, but the function of NrCAM in cochlear development is not well understood. Results: Throughout cochlear innervation, NrCAM is detectable on spiral ganglion neuron (SGN) afferent and olivocochlear efferent fibers, and on the membranes of developing hair and supporting cells. Neonatal Nrcam‐null cochleae show errors in type II SGN fasciculation, reduced efferent innervation, and defects in the stereotyped packing of hair and supporting cells. Nrcam loss also leads to dramatic changes in the profiles of presynaptic afferent and efferent synaptic markers at the time of hearing onset. Despite these numerous developmental defects, Nrcam‐null adults do not show defects in auditory acuity, and by postnatal day 21, the developmental deficits in ribbon synapse distribution and sensory domain structure appear to have been corrected. Conclusions: NrCAM is expressed by several neural and sensory epithelial subtypes within the developing cochlea, and the loss of Nrcam confers numerous, but nonpermanent, developmental defects in innervation and sensory domain patterning. Developmental Dynamics 247:934–950, 2018. © 2018 Wiley Periodicals, Inc. Key Findings NrCAM is expressed by spiral ganglion afferents, olivocochlear efferents, and hair and supporting cells in the developing cochlea. Loss of Nrcam confers numerous developmental defects in the cochlea, including defects in type II spiral ganglion neuron fasciculation, efferent connectivity, and sensory domain patterning. Loss of Nrcam also confers altered profiles of afferent and efferent synapses in the cochlea around the time of hearing onset.