Spiral Ganglion Neuron Projection Development to the Hindbrain in Mice Lacking Peripheral and/or Central Target Differentiation.

Karen L Elliott,Ning Pan,Bernd Fritzsch,Jennifer Kersigo,Israt Jahan

doi:10.3389/fncir.2017.00025

Abstract

We investigate the importance of the degree of peripheral or central target differentiation for mouse auditory afferent navigation to the organ of Corti and auditory nuclei in three different mouse models: first, a mouse in which the differentiation of hair cells, but not central auditory nuclei neurons is compromised (Atoh1-cre; Atoh1f/f); second, a mouse in which hair cell defects are combined with a delayed defect in central auditory nuclei neurons (Pax2-cre; Atoh1f/f), and third, a mouse in which both hair cells and central auditory nuclei are absent (Atoh1−/−). Our results show that neither differentiated peripheral nor the central target cells of inner ear afferents are needed (hair cells, cochlear nucleus neurons) for segregation of vestibular and cochlear afferents within the hindbrain and some degree of base to apex segregation of cochlear afferents. These data suggest that inner ear spiral ganglion neuron processes may predominantly rely on temporally and spatially distinct molecular cues in the region of the targets rather than interaction with differentiated target cells for a crude topological organization. These developmental data imply that auditory neuron navigation properties may have evolved before auditory nuclei.

Highlights

Experimental tracing of developing afferent innervation from individual end organs to the brain show initially segregated projections of all major sensory organs (Fritzsch et al, 2005a) and spatio-temporal segregation of afferent projections of vestibular and cochlear endorgans to the brainstem (Fritzsch et al, 2015; Dabdoub and Fritzsch, 2016)
Discrete topological projections to the cochlear nuclei are established at least 2 weeks before onset of hearing and 1 week before afferent activity is found in these neurons and adjacent cells (Wang et al, 2015), indicating that molecular cues, combined with the timing of arrival, can generate at least a crude cochleotopic map
It remains unclear how such molecular cues relate to developing hair cells and developing cochlear nuclei or whether these cues are intrinsic to the afferents or mediated in part by differentiating cochlear nucleus neurons and/or hair cells

Summary

Introduction

Experimental tracing of developing afferent innervation from individual end organs to the brain show initially segregated projections of all major sensory organs (Fritzsch et al, 2005a) and spatio-temporal segregation of afferent projections of vestibular and cochlear endorgans to the brainstem (Fritzsch et al, 2015; Dabdoub and Fritzsch, 2016). Discrete topological projections to the cochlear nuclei are established at least 2 weeks before onset of hearing and 1 week before afferent activity is found in these neurons and adjacent cells (Wang et al, 2015), indicating that molecular cues, combined with the timing of arrival, can generate at least a crude cochleotopic map. It remains unclear how such molecular cues relate to developing hair cells and developing cochlear nuclei or whether these cues are intrinsic to the afferents or mediated in part by differentiating cochlear nucleus neurons and/or hair cells

Methods

Results

Conclusion