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dock8 deficiency attenuates microglia colonization in early zebrafish larvae

Microglia are tissue-resident macrophages that carry out immune functions in the brain. The deficiency or dysfunction of microglia has been implicated in many neurodegenerative disorders. DOCK8, a member of the DOCK family, functions as a guanine nucleotide exchange factor and plays key roles in imm...

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Detalles Bibliográficos
Autores principales: Wu, Linxiu, Xue, Rongtao, Chen, Jiahao, Xu, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386030/
https://www.ncbi.nlm.nih.gov/pubmed/35977943
http://dx.doi.org/10.1038/s41420-022-01155-6
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author Wu, Linxiu
Xue, Rongtao
Chen, Jiahao
Xu, Jin
author_facet Wu, Linxiu
Xue, Rongtao
Chen, Jiahao
Xu, Jin
author_sort Wu, Linxiu
collection PubMed
description Microglia are tissue-resident macrophages that carry out immune functions in the brain. The deficiency or dysfunction of microglia has been implicated in many neurodegenerative disorders. DOCK8, a member of the DOCK family, functions as a guanine nucleotide exchange factor and plays key roles in immune regulation and neurological diseases. The functions of DOCK8 in microglia development are not fully understood. Here, we generated zebrafish dock8 mutants by CRISPR/Cas9 genome editing and showed that dock8 mutations attenuate microglia colonization in the zebrafish midbrain at early larvae stages. In vivo time-lapse imaging revealed that the motility of macrophages was reduced in the dock8 mutant. We further found that cdc42/cdc42l, which encode the small GTPase activated by Dock8, also regulate microglia colonization in zebrafish. Collectively, our study suggests that the Dock8-Cdc42 pathway is required for microglia colonization in zebrafish larvae.
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spelling pubmed-93860302022-08-19 dock8 deficiency attenuates microglia colonization in early zebrafish larvae Wu, Linxiu Xue, Rongtao Chen, Jiahao Xu, Jin Cell Death Discov Article Microglia are tissue-resident macrophages that carry out immune functions in the brain. The deficiency or dysfunction of microglia has been implicated in many neurodegenerative disorders. DOCK8, a member of the DOCK family, functions as a guanine nucleotide exchange factor and plays key roles in immune regulation and neurological diseases. The functions of DOCK8 in microglia development are not fully understood. Here, we generated zebrafish dock8 mutants by CRISPR/Cas9 genome editing and showed that dock8 mutations attenuate microglia colonization in the zebrafish midbrain at early larvae stages. In vivo time-lapse imaging revealed that the motility of macrophages was reduced in the dock8 mutant. We further found that cdc42/cdc42l, which encode the small GTPase activated by Dock8, also regulate microglia colonization in zebrafish. Collectively, our study suggests that the Dock8-Cdc42 pathway is required for microglia colonization in zebrafish larvae. Nature Publishing Group UK 2022-08-17 /pmc/articles/PMC9386030/ /pubmed/35977943 http://dx.doi.org/10.1038/s41420-022-01155-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wu, Linxiu
Xue, Rongtao
Chen, Jiahao
Xu, Jin
dock8 deficiency attenuates microglia colonization in early zebrafish larvae
title dock8 deficiency attenuates microglia colonization in early zebrafish larvae
title_full dock8 deficiency attenuates microglia colonization in early zebrafish larvae
title_fullStr dock8 deficiency attenuates microglia colonization in early zebrafish larvae
title_full_unstemmed dock8 deficiency attenuates microglia colonization in early zebrafish larvae
title_short dock8 deficiency attenuates microglia colonization in early zebrafish larvae
title_sort dock8 deficiency attenuates microglia colonization in early zebrafish larvae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386030/
https://www.ncbi.nlm.nih.gov/pubmed/35977943
http://dx.doi.org/10.1038/s41420-022-01155-6
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AT xujin dock8deficiencyattenuatesmicrogliacolonizationinearlyzebrafishlarvae