title: Neurosensory development and cell fate determination in the human cochlea.
abstract: BACKGROUND
  Hearing depends on correct functioning of the cochlear hair cells, and their innervation by spiral ganglion neurons. Most of the insight into the embryological and molecular development of this sensory system has been derived from animal studies. In contrast, little is known about the molecular expression patterns and dynamics of signaling molecules during normal fetal development of the human cochlea. In this study, we investigated the onset of hair cell differentiation and innervation in the human fetal cochlea at various stages of development.
  
  
  RESULTS
  At 10 weeks of gestation, we observed a prosensory domain expressing SOX2 and SOX9/SOX10 within the cochlear duct epithelium. In this domain, hair cell differentiation was consistently present from 12 weeks, coinciding with downregulation of SOX9/SOX10, to be followed several weeks later by downregulation of SOX2. Outgrowing neurites from spiral ganglion neurons were found penetrating into the cochlear duct epithelium prior to hair cell differentiation, and directly targeted the hair cells as they developed. Ubiquitous Peripherin expression by spiral ganglion neurons gradually diminished and became restricted to the type II spiral ganglion neurons by 18 weeks. At 20 weeks, when the onset of human hearing is thought to take place, the expression profiles in hair cells and spiral ganglion neurons matched the expression patterns of the adult mammalian cochleae.
  
  
  CONCLUSIONS
  Our study provides new insights into the fetal development of the human cochlea, contributing to our understanding of deafness and to the development of new therapeutic strategies to restore hearing.
authors.forename: Heiko
authors.initials: H
authors.lastname: Locher
authors.forename: Johan H M
authors.initials: JH
authors.lastname: Frijns
authors.forename: Liesbeth
authors.initials: L
authors.lastname: van Iperen
authors.forename: John C M J
authors.initials: JC
authors.lastname: de Groot
authors.forename: Margriet A
authors.initials: MA
authors.lastname: Huisman
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, T-01-032, Einthovenweg 20, 2333 ZC Leiden, the Netherlands. lopes@lumc.nl.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Chuva de Sousa Lopes
mesh_terms: D002454:Cell Differentiation; D003051:Cochlea / Q000196:embryology* / Q000378:metabolism; D003053:Cochlear Duct / Q000196:embryology / Q000294:innervation; D005260:Female; D005333:Fetus; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000502:physiology; D006801:Humans; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000378:metabolism; D013136:Spiral Ganglion / Q000196:embryology / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; C527923:SOX10 protein, human; C527782:SOX2 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055748:SOXB1 Transcription Factors; D055757:SOXE Transcription Factors