Damage-responsive neuro-glial clusters coordinate the recruitment of dormant neural stem cells in Drosophila.

Simões, Anabel R; Neto, Marta; Alves, Carolina S; Santos, Mariana B; Fernández-Hernández, Ismael; Veiga-Fernandes, Henrique; Brea, David; Durá, Irene; Encinas, Juan M; Rhiner, Christa (2022). Damage-responsive neuro-glial clusters coordinate the recruitment of dormant neural stem cells in Drosophila. Developmental cell, 57(13), 1661-1675.e7. Elsevier 10.1016/j.devcel.2022.05.015

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Recruitment of stem cells is crucial for tissue repair. Although stem cell niches can provide important signals, little is known about mechanisms that coordinate the engagement of disseminated stem cells across an injured tissue. In Drosophila, adult brain lesions trigger local recruitment of scattered dormant neural stem cells suggesting a mechanism for creating a transient stem cell activation zone. Here, we find that injury triggers a coordinated response in neuro-glial clusters that promotes the spread of a neuron-derived stem cell factor via glial secretion of the lipocalin-like transporter Swim. Strikingly, swim is induced in a Hif1-α-dependent manner in response to brain hypoxia. Mammalian Swim (Lcn7) is also upregulated in glia of the mouse hippocampus upon brain injury. Our results identify a central role of neuro-glial clusters in promoting neural stem cell activation at a distance, suggesting a conserved function of the HIF1-α/Swim/Wnt module in connecting injury-sensing and regenerative outcomes.

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