Abstract

Balance orientation depends on the precise operation of the vestibular end organs and the vestibular ganglion neurons. Previous research on the assemblage of the neuronal network in the developing fetal vestibular organ has been limited to data from animal models. Insights into the molecular expression profiles and signaling moieties involved in embryological development of the human fetal inner ear have been limited. We present an investigation of the cells of the vestibular end organs with specific focus on the hair cell differentiation and innervation pattern using an uninterrupted series of unique specimens from gestational weeks 8–12. Nerve fibers positive for peripherin innervate the entire fetal crista and utricle. While in rodents only the peripheral regions of the cristae and the extra-striolar region of the statolithic organs are stained. At week 9, transcription factors PAX2 and PAX8 were observed in the hair cells whereas PAX6 was observed for the first time among the supporting cells of the cristae and the satellite glial cells of the vestibular ganglia. Glutamine synthetase, a regulator of the neurotransmitter glutamate, is strongly expressed among satellite glia cells, transitional zones of the utricle and supporting cells in the sensory epithelium. At gestational week 11, electron microscopic examination reveals bouton contacts at hair cells and first signs of the formation of a protocalyx at type I hair cells. Our study provides first-hand insight into the fetal development of the vestibular end organs as well as their pattern of innervation by means of immunohistochemical and EM techniques, with the aim of contributing toward our understanding of balance development.

Highlights

  • The human inner ear consists of both the vestibular and cochlear parts that form organs for balance and hearing

  • The membranous labyrinth in the inner ear contains a secluded epithelial layer that is diversified into specific regions containing sensory elements of the hair cells and supporting cells, and transmits information to local neurons ensheathed by Schwann cells and satellite glia

  • We found Pax2 expression previously in the fetal human cochlea in the spiral ganglion neurons (SGN) as well as in the inner hair cells (IHCs) indicating its role in the early maturation of the IHCs in comparison to the outer hair cells (OHC; Pechriggl et al, 2015)

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Summary

Introduction

The human inner ear consists of both the vestibular and cochlear parts that form organs for balance and hearing. They start to develop during embryogenesis from the primordial surface ectoderm into the membranous labyrinth during the third gestational week (O’Rahilly, 1963). This surface ectoderm differentiates into the otic placode, otic primordium, and the otic vesicle. There is a lack of comparative studies regarding the activation of these specific marker genes and their influence during the development of the vestibular organ and the cochlea. We used different molecular markers to characterize sensorineural progression from gestational week 8–12 in human embryogenesis

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