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Molecular mechanisms of neural stem cell activation following brain injury in Drosophila melanogaster
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The mammalian brain contains dormant neural stem cells that reside in a reversible state of quiescence. A diverse range of physiologic signals are known to regulate their activity resulting in the formation of new neuronal or glial cells in the adult brain. Much less is known about the signals that control neural stem cell activation upon brain injury. Here, we used the fruit fly Drosophila melanogaster as a genetic model to uncover the mechanisms which coordinate the recruitment of quiescent neural stem cells in response to local brain damage. Based on a transcriptional survey, we identified a set of specific factors that are highly regulated upon brain tissue damage in flies. We discovered that injury triggers a coordinated response in neuro-glial
clusters by promoting the spread of the stem cell factor Wg/Wnt from neurons to nearby neural stem cells via the secretion of the lipocalin-like transporter Swim released from glial cells. Our results show that Swim expression in glia, in turn, is induced in a hif- Į-dependent manner in response to tissue hypoxia caused by brain lesions. We also observe upregulation of the mammalian Swim (Lcn7) in glia of the mouse hippocampus upon brain injury. Our results identify a central role of neuro-glial cooperation in promoting neural stem cell activation at a distance, suggesting a conserved function of the Hif-1α/Swim/Wnt signaling axis in connecting injury-sensing and regenerative outcomes.
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Drosophila Stem cell