Cargando…
Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development
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 deve...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564925/ https://www.ncbi.nlm.nih.gov/pubmed/23393595 http://dx.doi.org/10.1371/journal.pone.0055609 |
_version_ | 1782258385560797184 |
---|---|
author | Kim, Hyung Jin Woo, Hae-Mi Ryu, Jihee Bok, Jinwoong Kim, Jin Woo Choi, Sang Back Park, Mi-Hyun Park, Hyun-Young Koo, Soo Kyung |
author_facet | Kim, Hyung Jin Woo, Hae-Mi Ryu, Jihee Bok, Jinwoong Kim, Jin Woo Choi, Sang Back Park, Mi-Hyun Park, Hyun-Young Koo, Soo Kyung |
author_sort | Kim, Hyung Jin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3564925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35649252013-02-07 Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development Kim, Hyung Jin Woo, Hae-Mi Ryu, Jihee Bok, Jinwoong Kim, Jin Woo Choi, Sang Back Park, Mi-Hyun Park, Hyun-Young Koo, Soo Kyung PLoS One Research Article 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. Public Library of Science 2013-02-05 /pmc/articles/PMC3564925/ /pubmed/23393595 http://dx.doi.org/10.1371/journal.pone.0055609 Text en © 2013 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kim, Hyung Jin Woo, Hae-Mi Ryu, Jihee Bok, Jinwoong Kim, Jin Woo Choi, Sang Back Park, Mi-Hyun Park, Hyun-Young Koo, Soo Kyung Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development |
title | Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development |
title_full | Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development |
title_fullStr | Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development |
title_full_unstemmed | Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development |
title_short | Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development |
title_sort | conditional deletion of pten leads to defects in nerve innervation and neuronal survival in inner ear development |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564925/ https://www.ncbi.nlm.nih.gov/pubmed/23393595 http://dx.doi.org/10.1371/journal.pone.0055609 |
work_keys_str_mv | AT kimhyungjin conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT woohaemi conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT ryujihee conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT bokjinwoong conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT kimjinwoo conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT choisangback conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT parkmihyun conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT parkhyunyoung conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment AT koosookyung conditionaldeletionofptenleadstodefectsinnerveinnervationandneuronalsurvivalininnereardevelopment |