| A dual function for canonical Wnt/β-catenin signaling in the developing mammalian cochlea. | |
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MedLine Citation:
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PMID: 23132246 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The canonical Wnt/β-catenin signaling pathway is known to play crucial roles in organogenesis by regulating both proliferation and differentiation. In the inner ear, this pathway has been shown to regulate the size of the otic placode from which the cochlea will arise; however, direct activity of canonical Wnt signaling as well as its function during cochlear mechanosensory hair cell development had yet to be identified. Using TCF/Lef:H2B-GFP reporter mice and transfection of an independent TCF/Lef reporter construct, we describe the pattern of canonical Wnt activity in the developing mouse cochlea. We show that prior to terminal mitosis, canonical Wnt activity is high in early prosensory cells from which hair cells and support cells will differentiate, and activity becomes reduced as development progresses. Using an in vitro model we demonstrate that Wnt/β-catenin signaling regulates both proliferation and hair cell differentiation within the developing cochlear duct. Inhibition of Wnt/β-catenin signaling blocks proliferation during early mitotic phases of development and inhibits hair cell formation in the differentiating organ of Corti. Conversely, activation increases the number of hair cells that differentiate and induces proliferation in prosensory cells, causing an expansion of the Sox2-positive prosensory domain. We further demonstrate that the induced proliferation of Sox2-positive cells may be mediated by the cell cycle regulator cyclin D1. Lastly, we provide evidence that the mitotic Sox2-positive cells are competent to differentiate into hair cells. Combined, our data suggest that Wnt/β-catenin signaling has a dual function in cochlear development, regulating both proliferation and hair cell differentiation. |
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Authors:
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Bonnie E Jacques; Chandrakala Puligilla; Rachel M Weichert; Anna Ferrer-Vaquer; Anna-Katerina Hadjantonakis; Matthew W Kelley; Alain Dabdoub |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 139 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-11-07 Completed Date: 2013-01-16 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 4395-404 Citation Subset: IM |
Affiliation:
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University of California San Diego, School of Medicine, Department of Surgery, Division of Otolaryngology, La Jolla, CA 92093-0666, USA. bjacques@ucsd.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation Cell Proliferation Cochlea / cytology, embryology*, metabolism Cyclin D1 / metabolism Green Fluorescent Proteins / genetics Hair Cells, Auditory / metabolism* Mice Mice, Transgenic Organ Culture Techniques Organ of Corti / embryology*, metabolism Organogenesis SOXB1 Transcription Factors / metabolism Wnt Proteins / metabolism* Wnt Signaling Pathway* beta Catenin / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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P30 CA23100/CA/NCI NIH HHS; R01DC011104/DC/NIDCD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/SOXB1 Transcription Factors; 0/Sox2 protein, mouse; 0/Wnt Proteins; 0/beta Catenin; 136601-57-5/Cyclin D1; 147336-22-9/Green Fluorescent Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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