Distribution and Development of Peripheral Glial Cells in the Human Fetal Cochlea

Heiko Locher,John C. M. J. de Groot,Johan H. M. Frijns,Liesbeth van Iperen,Margriet A. Huisman,Susana M. Chuva de Sousa Lopes,Bernd Sokolowski

doi:10.1371/journal.pone.0088066

Heiko Locher, John C. M. J. de Groot + Show 5 more

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https://doi.org/10.1371/journal.pone.0088066

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Abstract

The adult human cochlea contains various types of peripheral glial cells that envelop or myelinate the three different domains of the spiral ganglion neurons: the central processes in the cochlear nerve, the cell bodies in the spiral ganglia, and the peripheral processes in the osseous spiral lamina. Little is known about the distribution, lineage separation and maturation of these peripheral glial cells in the human fetal cochlea. In the current study, we observed peripheral glial cells expressing SOX10, SOX9 and S100B as early as 9 weeks of gestation (W9) in all three neuronal domains. We propose that these cells are the common precursor to both mature Schwann cells and satellite glial cells. Additionally, the peripheral glial cells located along the peripheral processes expressed NGFR, indicating a phenotype distinct from the peripheral glial cells located along the central processes. From W12, the spiral ganglion was gradually populated by satellite glial cells in a spatiotemporal gradient. In the cochlear nerve, radial sorting was accomplished by W22 and myelination started prior to myelination of the peripheral processes. The developmental dynamics of the peripheral glial cells in the human fetal cochlea is in support of a neural crest origin. Our study provides the first overview of the distribution and maturation of peripheral glial cells in the human fetal cochlea from W9 to W22.

Highlights

Schwann cells, the major type of peripheral glial cells (PGCs), envelop and/or myelinate the spiral ganglion neurons (SGNs) in the cochlea and are essential to normal hearing
To identify PGCs, we immunostained for SOX10, S100B and TUBB3 (Fig. 2A–H)
The pattern of PGC distribution that we observed in humans at the early gestational stages (W9-12) is in agreement with the hypothesis of a neural crest origin, with neural crest cells or early derivatives migrating along the cochlear nerve (CN) into the human cochlea and populating the SG

Summary

Introduction

The major type of peripheral glial cells (PGCs), envelop and/or myelinate the spiral ganglion neurons (SGNs) in the cochlea and are essential to normal hearing. Demyelinating diseases of the peripheral nervous system result in differences in the velocity of action potential propagation between individual nerve processes [1]. Depending on the degree of demyelination, this loss of neural synchrony leads to moderate sensorineural hearing loss or, if there is a complete conduction block, to deafness [2,3,4]. One major peripheral neuropathy affecting hearing is Charcot-Marie-Tooth disease, a genetically and clinically heterogeneous group of disorders which includes mutations in genes that are involved in myelination [5,6,7,8]. Other causes of demyelination of peripheral nerves, and potentially leading to sensorineural hearing loss, include autoimmune diseases such as the GuillainBarresyndrome, and infectious diseases such as leprosy [9,10,11,12]. Loss of myelin may be involved in the development of agerelated sensorineural hearing loss [13]

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