Early appearance of key transcription factors influence the spatiotemporal development of the human inner ear

Lejo Johnson Chacko,Helge Rask-Andersen,Rudolf Glueckert,Jozsef Dudas,Anneliese Schrott-Fischer,Natalie Fischer,Theresa Eberharter,Romed Hoermann,Consolato Sergi,Helga Fritsch

doi:10.1007/s00441-019-03115-6

Abstract

Expression patterns of transcription factors leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), transforming growth factor-β-activated kinase-1 (TAK1), SRY (sex-determining region Y)-box 2 (SOX2), and GATA binding protein 3 (GATA3) in the developing human fetal inner ear were studied between the gestation weeks 9 and 12. Further development of cochlear apex between gestational weeks 11 and 16 (GW11 and GW16) was examined using transmission electron microscopy. LGR5 was evident in the apical poles of the sensory epithelium of the cochlear duct and the vestibular end organs at GW11. Immunostaining was limited to hair cells of the organ of Corti by GW12. TAK1 was immune positive in inner hair cells of the organ of Corti by GW12 and colocalized with p75 neurotrophic receptor expression. Expression for SOX2 was confined primarily to the supporting cells of utricle at the earliest stage examined at GW9. Intense expression for GATA3 was presented in the cochlear sensory epithelium and spiral ganglia at GW9. Expression of GATA3 was present along the midline of both the utricle and saccule in the zone corresponding to the striolar reversal zone where the hair cell phenotype switches from type I to type II. The spatiotemporal gradient of the development of the organ of Corti was also evident with the apex of the cochlea forming by GW16. It seems that highly specific staining patterns of several transcriptions factors are critical in guiding the genesis of the inner ear over development. Our findings suggest that the spatiotemporal gradient in cochlear development extends at least until gestational week 16.

Highlights

Hearing impairments and balance disorders are major health conditions estimated to affect significant sections of the global population (Agrawal et al 2009; Bowl and Dawson 2018)
As previously reported (Johnson Chacko et al 2017), we examined the expression (Fig. 2c, g, k) of this low-affinity neurotrophin receptor colocalizing with transforming growth factor-β-activated kinase-1 (TAK1) (Fig. 2h) in both the inner hair cells (IHCs) and outer hair cells (OHCs) at GW12
Expression of the adult stem cell marker leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) was apparent in the fetal cochlea from the gestational week (GW) 11 and onwards (Fig. 1a–c)

Summary

Introduction

Hearing impairments and balance disorders are major health conditions estimated to affect significant sections of the global population (Agrawal et al 2009; Bowl and Dawson 2018). Because of the lack of regenerative capacity in the adult human cochlea, preservation of every single hair cell and spiral ganglion cell is vital (Liu et al 2015; Smeti et al 2012). Sustained efforts to understand processes underlying inner ear development using murine models have revealed roles for several quintessential transcription factors like leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) (Bramhall et al 2014), transforming growth factor-β-activated kinase-1 (TAK1) (Parker et al 2011), SOX2 (Dvorakova et al 2016), and GATA binding protein 3 (GATA3) (Karis et al 2001). The expression profiles of these transcriptional factors and their functionality in human inner ear development are not currently clear. Previous research had examined the expression profiles of the transcription factors SOX2, S0X9, and SOX10 in the cochlea anlage (Locher et al 2013). Monoclonal anti-nerve growth factor receptor (NGFR p75) clone ME20.4 LGR5

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Results

Conclusion