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.
Highlights
Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence
In the vertebrate skin or the liver, de-repression of YAP has been shown to promote stem cell proliferation[24]. Whether this is true in neural stem cells (NSCs) and whether changes in Yorkie/YAP activity are causative for altering growth and proliferation during normal central nervous system (CNS) development remains unclear
At 4 h after larval hatching (ALH) we observed a significant increase in NSCs cell diameter, which was present when restricting the expression to only larval stages using the GAL80ts system (Fig. 3e,f)
Summary
Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. The expression of Crumbs and Echinoid in glial cells and NSCs is nutrition-dependent, and their premature loss in glial cells is sufficient to initiate reactivation of NSCs. the Yorkie activity discriminates between quiescent and non-quiescent NSCs, placing the SHW as a major regulator of growth in cellular quiescence in Drosophila NSCs. Results Loss of Hippo signalling causes premature NSCs reactivation.
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