Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication

eLife

Benjamin Altenhein¹  Maria Losada Perez²  Elizabeth Connolly³  Alicia Hidalgo³  Marta Moreira³  Zidan Yang³  Jun Sun³  Neale J Harrison³  Alicia Gascón Gubieda³ 

[1] Institute of Zoology, University of Cologne, Cologne, Germany;Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain;Structural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United Kingdom;

关键词: Drosophila;    glial cell;    dilp6;    ia-2;    regeneration;    neurogenesis;   

DOI  :  10.7554/eLife.58756

来源: DOAJ

【 摘 要 】

Understanding how injury to the central nervous system induces de novo neurogenesis in animals would help promote regeneration in humans. Regenerative neurogenesis could originate from glia and glial neuron-glia antigen-2 (NG2) may sense injury-induced neuronal signals, but these are unknown. Here, we used Drosophila to search for genes functionally related to the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Both loss and over-expression of ia-2 induced neural stem cell gene expression, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic analysis and lineage tracing, we demonstrate that Ia-2 and Kon regulate Drosophila insulin-like peptide 6 (Dilp-6) to induce glial proliferation and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia and reprogrammes glia into neural stem cells for regeneration.

【 授权许可】

Unknown