Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication
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,...
Main Authors: | , , , , , , , , |
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eLife Sciences Publications Ltd
2021-02-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/58756 |
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author | Neale J Harrison Elizabeth Connolly Alicia Gascón Gubieda Zidan Yang Benjamin Altenhein Maria Losada Perez Marta Moreira Jun Sun Alicia Hidalgo |
author_facet | Neale J Harrison Elizabeth Connolly Alicia Gascón Gubieda Zidan Yang Benjamin Altenhein Maria Losada Perez Marta Moreira Jun Sun Alicia Hidalgo |
author_sort | Neale J Harrison |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-12T02:46:34Z |
format | Article |
id | doaj.art-b7fd9195a1f1444180a77a979b67e322 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T02:46:34Z |
publishDate | 2021-02-01 |
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record_format | Article |
series | eLife |
spelling | doaj.art-b7fd9195a1f1444180a77a979b67e3222022-12-22T03:51:09ZengeLife Sciences Publications LtdeLife2050-084X2021-02-011010.7554/eLife.58756Regenerative neurogenic response from glia requires insulin-driven neuron-glia communicationNeale J Harrison0https://orcid.org/0000-0001-6821-4089Elizabeth Connolly1https://orcid.org/0000-0002-5716-8889Alicia Gascón Gubieda2Zidan Yang3Benjamin Altenhein4Maria Losada Perez5Marta Moreira6https://orcid.org/0000-0002-4779-4077Jun Sun7https://orcid.org/0000-0002-1539-9937Alicia Hidalgo8https://orcid.org/0000-0001-8041-5764Structural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United KingdomStructural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United KingdomStructural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United KingdomStructural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United KingdomInstitute of Zoology, University of Cologne, Cologne, GermanyInstituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, SpainStructural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United KingdomStructural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United KingdomStructural Plasticity & Regeneration Group, School of Biosciences, University of Birmingham, Birmingham, United KingdomUnderstanding 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.https://elifesciences.org/articles/58756Drosophilaglial celldilp6ia-2regenerationneurogenesis |
spellingShingle | Neale J Harrison Elizabeth Connolly Alicia Gascón Gubieda Zidan Yang Benjamin Altenhein Maria Losada Perez Marta Moreira Jun Sun Alicia Hidalgo Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication eLife Drosophila glial cell dilp6 ia-2 regeneration neurogenesis |
title | Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication |
title_full | Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication |
title_fullStr | Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication |
title_full_unstemmed | Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication |
title_short | Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication |
title_sort | regenerative neurogenic response from glia requires insulin driven neuron glia communication |
topic | Drosophila glial cell dilp6 ia-2 regeneration neurogenesis |
url | https://elifesciences.org/articles/58756 |
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