title: Conditional deletion of pten leads to defects in nerve innervation and neuronal survival in inner ear development.
abstract: All cellular phenomena and developmental events, including inner ear development, are modulated through harmonized signaling networks. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor, is a major signaling component involved in cross talk with key regulators of development; i.e., Wnt, Notch, and bone morphogenetic proteins. Although Pten function has been studied in various systems, its role in inner ear development is poorly understood. Here, we used inner ear-specific Pten conditional knockout mice and examined the characteristics of the inner ear. In a detailed analysis of the phenotype, reduced cochlear turning and widened epithelia were observed. Phalloidin staining of sensory epithelium revealed that hair cell patterns were disturbed; i.e., additional rows of hair cells were discovered. The neural abnormality revealed a reduction in and disorganization of nerve fibers, including apoptosis at the neural precursor stage. Pten deficiency induced increased phosphorylation of Akt at Ser473. The elevation of inhibitory glycogen synthase kinase 3β Ser9 phosphorylation (pGSK3β) was sustained until the neuronal differentiation stage at embryonic day 14.5, instead of pGSK3β downregulation. This is the first report on the influence of Pten/Akt/GSK3β signaling on the development of spiral ganglia. These results suggest that Pten is required for the maintenance of neuroblast number, neural precursors, and differentiation in the inner ear.
authors: Center for Biomedical Sciences, National Institute of Health, Osong Health Technology Administration Complex 643, Yeonje-ri, Osong-eup, Cheongwon-gun, Chungcheongbuk-do, South Korea.
authors: Hyung Jin
authors: HJ
authors: Kim
authors: Hae-Mi
authors: HM
authors: Woo
authors: Jihee
authors: J
authors: Ryu
authors: Jinwoong
authors: J
authors: Bok
authors: Jin Woo
authors: JW
authors: Kim
authors: Sang Back
authors: SB
authors: Choi
authors: Mi-Hyun
authors: MH
authors: Park
authors: Hyun-Young
authors: HY
authors: Park
authors: Soo Kyung
authors: SK
authors: Koo
mesh_terms: D000818:Animals; D007758:Ear, Inner / Q000166:cytology* / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D006198:Hair Cells, Auditory / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D051059:PTEN Phosphohydrolase
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