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A regulatory transcriptional loop controls proliferation and differentiation in Drosophila neural stem cells

Yasugi, Tetsuo and Fischer, Anja and Jiang, Yanrui and Reichert, Heinrich and Knoblich, Juergen A.. (2014) A regulatory transcriptional loop controls proliferation and differentiation in Drosophila neural stem cells. PLoS ONE, Vol. 9, H. 5 , e97034.

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Official URL: http://edoc.unibas.ch/dok/A6263197

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Abstract

Neurogenesis is initiated by a set of basic Helix-Loop-Helix (bHLH) transcription factors that specify neural progenitors and allow them to generate neurons in multiple rounds of asymmetric cell division. The Drosophila Daughterless (Da) protein and its mammalian counterparts (E12/E47) act as heterodimerization factors for proneural genes and are therefore critically required for neurogenesis. Here, we demonstrate that Da can also be an inhibitor of the neural progenitor fate whose absence leads to stem cell overproliferation and tumor formation. We explain this paradox by demonstrating that Da induces the differentiation factor Prospero (Pros) whose asymmetric segregation is essential for differentiation in one of the two daughter cells. Da co-operates with the bHLH transcription factor Asense, whereas the other proneural genes are dispensible. After mitosis, Pros terminates Asense expression in one of the two daughter cells. In da mutants, pros is not expressed, leading to the formation of lethal transplantable brain tumors. Our results define a transcriptional feedback loop that regulates the balance between self-renewal and differentiation in Drosophila optic lobe neuroblasts. They indicate that initiation of a neural differentiation program in stem cells is essential to prevent tumorigenesis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Molecular Zoology (Reichert)
UniBasel Contributors:Reichert, Heinrich
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:31 Aug 2018 06:39
Deposited On:20 Jun 2014 07:56

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