A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects

The mammalian central nervous system (CNS) exhibits limited regenerative capacity and the mechanisms that mediate its regeneration are not fully understood. Here, we present a novel experimental design to damage the CNS by using a contusion injury paradigm. The design of this protocol allows the stu...

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Authors: Losada-Pérez, María, García-Guillén, Nuria, Casas-Tinto, Sergio
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/257700
Online Access:http://hdl.handle.net/10261/257700
Access Level:Open access
Keyword:CNS damage
Glia
Immune response
JNK
Macrophages
Regeneration
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spelling A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspectsLosada-Pérez, MaríaGarcía-Guillén, NuriaCasas-Tinto, SergioCNS damageGliaImmune responseJNKMacrophagesRegenerationThe mammalian central nervous system (CNS) exhibits limited regenerative capacity and the mechanisms that mediate its regeneration are not fully understood. Here, we present a novel experimental design to damage the CNS by using a contusion injury paradigm. The design of this protocol allows the study of long-term and short-term cellular responses, including those of the CNS and the immune system, and of any implications regarding functional recovery. We demonstrate for the first time that adult Drosophila melanogaster glial cells undergo spontaneous functional recovery following crush injury. This crush injury leads to an intermediate level of functional recovery after damage, which is ideal to screen for genes that facilitate or prevent the regeneration process. Here, we validate this model and analyse the immune responses of glial cells as a central regulator of functional regeneration. Additionally, we demonstrate that glial cells and macrophages contribute to functional regeneration through mechanisms involving the Jun N-terminal kinase (JNK) pathway and the Drosophila protein Draper (Drpr), characteristic of other neural injury paradigms. We show that macrophages are recruited to the injury site and are required for functional recovery. Further, we show that the proteins Grindelwald and Drpr in Drosophila glial cells mediate activation of JNK, and that expression of drpr is dependent on JNK activation. Finally, we link neuron-glial communication and the requirement of neuronal vesicular transport to regulation of the JNK pathway and functional recovery.This work was supported by the Ministerio de Ciencia y Tecnología (grant number: PID2019-110116GB-100, MICINN to S.C.T.), the Consejo Superior de Investigaciones Científicas (CSIC, grant number: LINKA 20268 to S.C.T.) and ́Fellowship from the Comunidad de Madrid (grant number: 2016-T2-BMD-1295 to M.L.-P.)Company of BiologistsMinisterio de Ciencia y Tecnología (España)Consejo Superior de Investigaciones Científicas (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/257700reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MICINN/ Ministerio de Ciencia y Tecnología PID2019-110116GB-100/info:eu-repo/grantAgreement/CSIC/ Consejo Superior de Investigaciones Científicas LINKA 20268 to S.C.T./info:eu-repo/grantAgreement/Comunidad de Madrid 2016-T2-BMD-1295 to M.L.-P.//http://dx.doi.org/10.1242/DMM.044669Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2577002026-05-22T06:33:51Z
dc.title.none.fl_str_mv A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
title A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
spellingShingle A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
Losada-Pérez, María
CNS damage
Glia
Immune response
JNK
Macrophages
Regeneration
title_short A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
title_full A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
title_fullStr A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
title_full_unstemmed A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
title_sort A novel injury paradigm in the central nervous system of adult Drosophila: Molecular, cellular and functional aspects
dc.creator.none.fl_str_mv Losada-Pérez, María
García-Guillén, Nuria
Casas-Tinto, Sergio
author Losada-Pérez, María
author_facet Losada-Pérez, María
García-Guillén, Nuria
Casas-Tinto, Sergio
author_role author
author2 García-Guillén, Nuria
Casas-Tinto, Sergio
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia y Tecnología (España)
Consejo Superior de Investigaciones Científicas (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv CNS damage
Glia
Immune response
JNK
Macrophages
Regeneration
topic CNS damage
Glia
Immune response
JNK
Macrophages
Regeneration
description The mammalian central nervous system (CNS) exhibits limited regenerative capacity and the mechanisms that mediate its regeneration are not fully understood. Here, we present a novel experimental design to damage the CNS by using a contusion injury paradigm. The design of this protocol allows the study of long-term and short-term cellular responses, including those of the CNS and the immune system, and of any implications regarding functional recovery. We demonstrate for the first time that adult Drosophila melanogaster glial cells undergo spontaneous functional recovery following crush injury. This crush injury leads to an intermediate level of functional recovery after damage, which is ideal to screen for genes that facilitate or prevent the regeneration process. Here, we validate this model and analyse the immune responses of glial cells as a central regulator of functional regeneration. Additionally, we demonstrate that glial cells and macrophages contribute to functional regeneration through mechanisms involving the Jun N-terminal kinase (JNK) pathway and the Drosophila protein Draper (Drpr), characteristic of other neural injury paradigms. We show that macrophages are recruited to the injury site and are required for functional recovery. Further, we show that the proteins Grindelwald and Drpr in Drosophila glial cells mediate activation of JNK, and that expression of drpr is dependent on JNK activation. Finally, we link neuron-glial communication and the requirement of neuronal vesicular transport to regulation of the JNK pathway and functional recovery.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/257700
url http://hdl.handle.net/10261/257700
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MICINN/ Ministerio de Ciencia y Tecnología PID2019-110116GB-100/
info:eu-repo/grantAgreement/CSIC/ Consejo Superior de Investigaciones Científicas LINKA 20268 to S.C.T./
info:eu-repo/grantAgreement/Comunidad de Madrid 2016-T2-BMD-1295 to M.L.-P.//
http://dx.doi.org/10.1242/DMM.044669
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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