Regeneration in the Fly Brain: Wake-Up Signals for Quiescent Neural Stem Cells

Dr. Christa Rhiner , Champalimaud Foundation, Portugal, will join Skin Ageing & Challenges 2022 to give a presentation about the “Regeneration in the Fly Brain: Wake-Up Signals for Quiescent Neural Stem Cells”.

Injury is known to stimulate diverse forms of tissue plasticity, including the activation of tissue-resident stem cells that fuel tissue regeneration. While 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, brain lesions trigger local recruitment of scattered dormant neural stem cells suggesting a mechanism for creating a transient stem cell activation zone in the adult brain. Dr. Rhiner and her team therefore took advantage of genetically versatile Drosophila to elucidate how injury-induced changes in the adult fly brain lead to activation of quiescent neural stem cells.

They uncovered that brain lesions trigger a coordinated response in local neuro-glial clusters that promotes the spread of a neuron-derived stem cell factor (Wg) via glial secretion of the lipocalin-like transporter Swim.Swim expression in glia, in turn, is induced in a Hif1-alpha-dependent manner downstream of transient brain hypoxia. They show that increased levels of Wg/Wnt signaling in neural stem cells is sufficient to trigger their proliferation.

Interestingly, Dr. Rhiner and her team found that mammalian Swim (Lcn7) is also upregulated in glia in the mouse hippocampus upon brain injury. Their results therefore reveal a central role of neuro-glial clusters in promoting neural stem cell activation at a distance suggesting a conserved function of the HIF1-alpha/Swim/Wnt module in connecting injury-sensing and regenerative outcomes.