Insulin-like growth factor signaling regulates the timing of sensory cell differentiation in the mouse cochlea

Takayuki Okano, Shouhong Xuan, Matthew W. Kelley

研究成果: ジャーナルへの寄稿学術論文査読

63 被引用数 (Scopus)

抄録

The mammalian auditory sensory epithelium, the organ of Corti, is a highly ordered cellular structure that comprises two types of auditory hair cells and several types of nonsensory supporting cells. During embryogenesis, a stereotyped sequence of cellular and molecular events is required for its development. These processes are assumed to be regulated by multiple growth and transcription factors. However, the majority of these factors have not been identified. One potential regulator of cochlear development is the insulinlike growth factor (IGF) signaling family. To examine the roles of the IGF pathway in inner ear formation, cochleae from Igf1r mutant mice were analyzed. Deletion of Igf1r leads to several changes in inner ear development including a shortened cochlear duct, a decrease in the total number of cochlear hair cells, and defects in the formation of the semicircular canals. In addition, maturation of the cochlear sensory epithelium was delayed at the transition point between cellular proliferation and differentiation. To determine the molecular basis for these defects, inhibition of IGF signaling was replicated pharmacologically in vitro. Results indicated that IGF signaling regulates cochlear length and hair cell number as well as Atoh1 expression through the phosphatidylinositol 3-kinase/Akt signaling pathway. These results demonstrate novel roles for IGF signaling in inner ear development including regulation of vestibular formation, length of the cochlear duct, and the number of cochlear hair cells. The results also provide new insights regarding the pathological processes that underlie auditory defects in the absence of IGF signaling in both humans and mice.

本文言語英語
ページ(範囲)18104-18118
ページ数15
ジャーナルJournal of Neuroscience
31
49
DOI
出版ステータス出版済み - 2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学一般

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