4.7 Article

Hepatocyte Growth Factor-c-MET Signaling Mediates the Development of Nonsensory Structures of the Mammalian Cochlea and Hearing

期刊

JOURNAL OF NEUROSCIENCE
卷 36, 期 31, 页码 8200-8209

出版社

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4410-15.2016

关键词

auditory; melanocyte; neural crest; receptor tyrosine kinase; stria vascularis

资金

  1. Bundy Foundation
  2. Hearing and Health Foundation
  3. National Institutes of Health Grant [DC012085]
  4. Simms/Mann Chair in Developmental Neurogenetics
  5. University of Southern California (USC) Caruso Department of Otolaryngology-Head and Neck Surgery
  6. House Ear Institute

向作者/读者索取更多资源

The stria vascularis is a nonsensory structure that is essential for auditory hair cell function by maintaining potassium concentration of the scala media. During mouse embryonic development, a subpopulation of neural crest cell-derived melanocytes migrates and incorporates into a subregion of the cochlear epithelium, forming the intermediate cell layer of the stria vascularis. The relation of this developmental process to stria vascularis function is currently unknown. In characterizing the molecular differentiation of developing peripheral auditory structures, we discovered that hepatocyte growth factor (Hgf) is expressed in the future stria vascularis of the cochlear epithelium. Its receptor tyrosine kinase, c-Met, is expressed in the cochlear epithelium and melanocyte-derived intermediate cells in the stria vascularis. Genetic dissection of HGF signaling via c-MET reveals that the incorporation of the melanocytes into the future stria vascularis of the cochlear duct requires c-MET signaling. In addition, inactivation of either the ligand or receptor developmentally resulted in a profound hearing loss at young adult stages. These results suggest a novel connection between HGF signaling and deafness via melanocyte deficiencies.

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