Document Detail

Eya1-Six1 interaction is sufficient to induce hair cell fate in the cochlea by activating Atoh1 expression in cooperation with Sox2.
MedLine Citation:
PMID:  22340499     Owner:  NLM     Status:  MEDLINE    
Inner-ear hair cell differentiation requires Atoh1 function, while Eya1, Six1, and Sox2 are coexpressed in sensory progenitors and mutations in these genes cause sensorineural hearing loss. However, how these genes are linked functionally and the transcriptional networks controlling hair cell induction remain unclear. Here, we show (1) that Eya1/Six1 are necessary for hair cell development, and their coexpression in mouse cochlear explants is sufficient to induce hair cell fate in the nonsensory epithelium expressing low-level Sox2 by activating not only Atoh1-dependent but also Atoh1-independent pathways and (2) that both pathways induce Pou4f3 to promote hair cell differentiation. Sox2 cooperates with Eya1/Six1 to synergistically activate Atoh1 transcription via direct binding to the conserved Sox- and Six-binding sites in Atoh1 enhancers, and these proteins physically interact. Our findings demonstrate that direct and cooperative interactions between the Sox2, Six1, and Eya1 proteins coordinate Atoh1 expression to specify hair cell fate.
Mohi Ahmed; Elaine Y M Wong; Jianbo Sun; Jinshu Xu; Feng Wang; Pin-Xian Xu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Developmental cell     Volume:  22     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-05-01     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  377-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism*
Blotting, Western
Cell Differentiation
Chromatin Immunoprecipitation
Cochlea / cytology,  metabolism*
Electrophoretic Mobility Shift Assay
Embryo, Mammalian / cytology,  metabolism
Gene Expression Regulation, Developmental
Hair Cells, Auditory / metabolism*
Homeodomain Proteins / genetics,  metabolism*
Immunoenzyme Techniques
Intracellular Signaling Peptides and Proteins / genetics,  metabolism*
Mutation / genetics
Nuclear Proteins / genetics,  metabolism*
Protein Tyrosine Phosphatases / genetics,  metabolism*
SOXB1 Transcription Factors / genetics,  metabolism*
Grant Support
DC005824-S1/DC/NIDCD NIH HHS; R01 DC005824/DC/NIDCD NIH HHS; R01 DC005824/DC/NIDCD NIH HHS; R01 DC005824-08S1/DC/NIDCD NIH HHS; R01 DC005824-09/DC/NIDCD NIH HHS; R01 DC005824-10/DC/NIDCD NIH HHS
Reg. No./Substance:
0/Atoh1 protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Homeodomain Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Nuclear Proteins; 0/SOXB1 Transcription Factors; 0/Six1 protein, mouse; 0/Sox2 protein, mouse; EC protein, mouse; EC Tyrosine Phosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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