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

• Published in: Developmental cell 2022-07, Vol.57 (13), p.1661-1675.e7
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: brain injury; damage-responsive; Drosophila; HIF1-α; hypoxia; neuro-glial cooperation; quiescent neural stem cells; Swim/Lcn7
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2022.05.015

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. [Display omitted] •Brain lesions trigger a local coordinated response in neuro-glial clusters•Glia produce the secreted transporter Swim upon transient brain hypoxia•Swim promotes Wg/Wnt distribution in the injured brain domain•Wg/Wnt signaling drives proliferation of normally quiescent neural stem cells Simões et al. investigate adult brain plasticity in response to injury. They describe a mechanism by which neurons and glia cooperate to reactivate quiescent neural progenitors and promote a regenerative response. The process is based on a Hif1-α/Swim/Wnt signaling module that connects injury sensing to stem cell recruitment.