title: The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells.
abstract: Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. Drosophila neural stem cells (NSCs) are quiescent at early larval stages, when they are reactivated in response to metabolic changes. Here we report that cell-contact inhibition of growth through the canonical Hippo signalling pathway maintains NSC quiescence. Loss of the core kinases hippo or warts leads to premature nuclear localization of the transcriptional co-activator Yorkie and initiation of growth and proliferation in NSCs. Yorkie is necessary and sufficient for NSC reactivation, growth and proliferation. The Hippo pathway activity is modulated via inter-cellular transmembrane proteins Crumbs and Echinoid that are both expressed in a nutrient-dependent way in niche glial cells and NSCs. Loss of crumbs or echinoid in the niche only is sufficient to reactivate NSCs. Finally, we provide evidence that the Hippo pathway activity discriminates quiescent from non-quiescent NSCs in the Drosophila nervous system.
authors.affiliation: Institute of Genetics, Johannes Gutenberg University, 55099 Mainz, Germany.
authors.forename: Rouven
authors.initials: R
authors.lastname: Ding
authors.affiliation: Institute of Genetics, Johannes Gutenberg University, 55099 Mainz, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Weynans
authors.affiliation: School of Biomedical and Healthcare Sciences, Plymouth University, PL4 8AA Plymouth, UK.
authors.forename: Torsten
authors.initials: T
authors.lastname: Bossing
authors.affiliation: Peninsula School of Medicine, Plymouth University, PL6 8BU Plymouth, UK.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Barros
authors.affiliation: Institute of Genetics, Johannes Gutenberg University, 55099 Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Berger
mesh_terms: D000818:Animals; D004330:Drosophila / Q000166:cytology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction / Q000502:physiology*; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases
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