English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/129590
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

The retinal determination gene dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex

AuthorsBras-Pereira, Catarina ; Casares, Fernando ; Janody, Florence
KeywordsHomothorax
Organ growth
Progenitor proliferation
Dachshund
Yorkie
Drosophila eye development
Issue Date2015
PublisherCompany of Biologists
CitationDevelopment 142(8): 1470-1479 (2015)
AbstractThe Drosophila transcriptional co-activator protein Yorkie and its vertebrate orthologs YAP and TAZ are potent oncogenes, whose activity is normally kept in check by the upstream Hippo kinase module. Upon its translocation into the nucleus, Yorkie forms complexes with several tissue-specific DNA-binding partners, which help to define the tissue-specific target genes of Yorkie. In the progenitor cells of the eye imaginal disc, the DNA-binding transcription factor Homothorax is required for Yorkie-promoted proliferation and survival through regulation of the bantam microRNA (miRNA). The transit from proliferating progenitors to cell cycle quiescent precursors is associated with the progressive loss of Homothorax and gain of Dachshund, a nuclear protein related to the Sno/Ski family of co-repressors. We have identified Dachshund as an inhibitor of Homothorax-Yorkie-mediated cell proliferation. Loss of dachshund induces Yorkie-dependent tissue overgrowth. Conversely, overexpressing dachshund inhibits tissue growth, prevents Yorkie or Homothorax-mediated cell proliferation of disc epithelia and restricts the transcriptional activity of the Yorkie-Homothorax complex on the bantam enhancer in Drosophila cells. In addition, Dachshund collaborates with the Decapentaplegic receptor Thickveins to repress Homothorax and Cyclin B expression in quiescent precursors. The antagonistic roles of Homothorax and Dachshund in Yorkie activity, together with their mutual repression, ensure that progenitor and precursor cells are under distinct proliferation regimes. Based on the crucial role of the human dachshund homolog DACH1 in tumorigenesis, our work suggests that DACH1 might prevent cellular transformation by limiting the oncogenic activity of YAP and/or TAZ.
URIhttp://hdl.handle.net/10261/129590
DOI10.1242/dev.113340
Identifiersdoi: 10.1242/dev.113340
e-issn: 1477-9129
issn: 0950-1991
Appears in Collections:(CABD) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.