| Prox1 interacts with Atoh1 and Gfi1, and regulates cellular differentiation in the inner ear sensory epithelia. | |
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MedLine Citation:
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PMID: 18652815 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inner ear hair cells and supporting cells arise from common precursors and, in mammals, do not show phenotypic conversion. Here, we studied the role of the homeodomain transcription factor Prox1 in the inner ear sensory epithelia. Adenoviral-mediated Prox1 transduction into hair cells in explant cultures led to strong repression of Atoh1 and Gfi1, two transcription factors critical for hair cell differentiation and survival. Luciferase assays showed that Prox1 can repress transcriptional activity of Gfi1 independently of Atoh1. Prox1 transduction into cochlear outer hair cells resulted in degeneration of these cells, consistent with the known phenotype of Gfi1-deficient mice. These results together with the widespread expression of endogenous Prox1 within the population of inner ear supporting cells point to the role for Prox1 in antagonizing the hair cell phenotype in these non-sensory cells. Further, in vivo analyses of hair cells from Gfi1-deficient mice suggest that the cyclin-dependent kinase inhibitor p57(Kip2) mediates the differentiation- and survival-promoting functions of Gfi1. These data reveal novel gene interactions and show that these interactions regulate cellular differentiation within the inner ear sensory epithelia. The data point to the tight regulation of phenotypic characteristics of hair cells and supporting cells. |
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Authors:
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Anna Kirjavainen; Marilin Sulg; Florian Heyd; Kari Alitalo; Seppo Ylä-Herttuala; Tarik Möröy; Tatiana V Petrova; Ulla Pirvola |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-09 |
Journal Detail:
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Title: Developmental biology Volume: 322 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2008 Oct |
Date Detail:
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Created Date: 2008-10-16 Completed Date: 2008-11-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 33-45 Citation Subset: IM |
Affiliation:
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Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Animals Apoptosis / physiology Basic Helix-Loop-Helix Transcription Factors / metabolism* Cell Differentiation / genetics, physiology* Cells, Cultured Cochlea / cytology, embryology, metabolism Cyclin-Dependent Kinase Inhibitor p57 / genetics, metabolism DNA-Binding Proteins / metabolism* Ear, Inner / cytology, embryology* Epithelial Cells / cytology, physiology* Gene Expression Regulation, Developmental Gene Transfer Techniques Genes, Reporter Hair Cells, Auditory / cytology, metabolism, virology Homeodomain Proteins / genetics, metabolism, physiology* Immunohistochemistry Mice Mice, Knockout NIH 3T3 Cells Organ Culture Techniques Saccule and Utricle / cytology, embryology, metabolism Transcription Factors / metabolism* Tumor Suppressor Proteins / genetics, metabolism, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Atoh1 protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Cdkn1c protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p57; 0/DNA-Binding Proteins; 0/Gfi1 protein, mouse; 0/Homeodomain Proteins; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 0/prospero-related homeobox 1 protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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