Document Detail

Prox1 interacts with Atoh1 and Gfi1, and regulates cellular differentiation in the inner ear sensory epithelia.
MedLine Citation:
PMID:  18652815     Owner:  NLM     Status:  MEDLINE    
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.
Anna Kirjavainen; Marilin Sulg; Florian Heyd; Kari Alitalo; Seppo Ylä-Herttuala; Tarik Möröy; Tatiana V Petrova; Ulla Pirvola
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-09
Journal Detail:
Title:  Developmental biology     Volume:  322     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-16     Completed Date:  2008-11-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  33-45     Citation Subset:  IM    
Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
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MeSH Terms
Adenoviridae / genetics
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*
Mice, Knockout
NIH 3T3 Cells
Organ Culture Techniques
Saccule and Utricle / cytology,  embryology,  metabolism
Transcription Factors / metabolism*
Tumor Suppressor Proteins / genetics,  metabolism,  physiology*
Reg. No./Substance:
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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