The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells

Abstract

<jats:title>Abstract</jats:title><jats:p>Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. <jats:italic>Drosophila</jats:italic> 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 <jats:italic>hippo</jats:italic> or <jats:italic>warts</jats:italic> 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 <jats:italic>crumbs</jats:italic> or <jats:italic>echinoid</jats:italic> 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 <jats:italic>Drosophila</jats:italic> nervous system.</jats:p>