title: Development of the stria vascularis and potassium regulation in the human fetal cochlea: Insights into hereditary sensorineural hearing loss.
abstract: Sensorineural hearing loss (SNHL) is one of the most common congenital disorders in humans, afflicting one in every thousand newborns. The majority is of heritable origin and can be divided in syndromic and nonsyndromic forms. Knowledge of the expression profile of affected genes in the human fetal cochlea is limited, and as many of the gene mutations causing SNHL likely affect the stria vascularis or cochlear potassium homeostasis (both essential to hearing), a better insight into the embryological development of this organ is needed to understand SNHL etiologies. We present an investigation on the development of the stria vascularis in the human fetal cochlea between 9 and 18 weeks of gestation (W9-W18) and show the cochlear expression dynamics of key potassium-regulating proteins. At W12, MITF+/SOX10+/KIT+ neural-crest-derived melanocytes migrated into the cochlea and penetrated the basement membrane of the lateral wall epithelium, developing into the intermediate cells of the stria vascularis. These melanocytes tightly integrated with Na+/K+-ATPase-positive marginal cells, which started to express KCNQ1 in their apical membrane at W16. At W18, KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30 were expressed in the cells in the outer sulcus, but not in the spiral ligament. Finally, we investigated GJA1/CX43 and GJE1/CX23 expression, and suggest that GJE1 presents a potential new SNHL associated locus. Our study helps to better understand human cochlear development, provides more insight into multiple forms of hereditary SNHL, and suggests that human hearing does not commence before the third trimester of pregnancy.
authors: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.|Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.
authors: Heiko
authors: H
authors: Locher
authors: Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.
authors: John C M J
authors: JC
authors: de Groot
authors: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.
authors: Liesbeth
authors: L
authors: van Iperen
authors: Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.
authors: Margriet A
authors: MA
authors: Huisman
authors: Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.
authors: Johan H M
authors: JH
authors: Frijns
authors: Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, 2333 ZA, the Netherlands.|Department for Reproductive Medicine, Ghent University Hospital, 9000, Ghent, Belgium.
authors: Susana M
authors: SM
authors: Chuva de Sousa Lopes
mesh_terms: D002465:Cell Movement; D003051:Cochlea / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D000072259:Connexin 26; D000075302:Connexin 30; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051657:KCNQ1 Potassium Channel / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000502:physiology; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D018613:Microscopy, Confocal; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013316:Stria Vascularis / Q000166:cytology / Q000502:physiology*; D000098854:Kcnj10 Channel
chemical_list: D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C500216:GJA1 protein, human; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; C000609019:GJE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D000098854:Kcnj10 Channel; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D024661:Potassium Channels, Inwardly Rectifying; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D000072259:Connexin 26; D019009:Proto-Oncogene Proteins c-kit; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium
keywords: development; human; melanocytes; sensorineural hearing loss; stria vascularis