dock8 deficiency attenuates microglia colonization in early zebrafish larvae.
dock8 deficiency attenuates microglia colonization in early zebrafish larvae.
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DOI：
10.1038/s41420-022-01155-6
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发表时间：
2022-08-17
影响因子：
7
通讯作者：
Xu, Jin
中科院分区：
文献类型：
--
作者：
Wu, Linxiu;Xue, Rongtao;Chen, Jiahao;Xu, Jin
小胶质细胞是组织内的巨噬细胞，在大脑中执行免疫功能。小胶质细胞的缺乏或功能障碍与许多神经退行性疾病有关。DOCK8是DOCK家族成员之一，作为鸟嘌呤核苷酸交换因子，在免疫调节和神经系统疾病中发挥关键作用。DOCK8在小胶质细胞发育中的功能尚不完全清楚。在这里，我们通过CRISPR/Cas9基因组编辑生成了斑马鱼dock8突变体，并表明dock8突变在斑马鱼幼虫早期阶段减弱了小胶质细胞在中脑的定植。体内延时成像显示dock8突变体中巨噬细胞的运动性降低。我们进一步发现，编码Dock8激活的小GTPase的cdc42/cdc42l也调节斑马鱼小胶质细胞的定植。总之，我们的研究表明Dock8-Cdc42通路是斑马鱼幼体小胶质细胞定植所必需的。
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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影响因子：
25
作者：
Kierdorf, Katrin;Erny, Daniel;Prinz, Marco
通讯作者：
Prinz, Marco
影响因子：
7.7
作者：
He S;Chen J;Jiang Y;Wu Y;Zhu L;Jin W;Zhao C;Yu T;Wang T;Wu S;Lin X;Qu JY;Wen Z;Zhang W;Xu J
通讯作者：
Xu J
DOI：
10.1083/jcb.141.5.1147
发表时间：
1998-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Allen WE;Zicha D;Ridley AJ;Jones GE
通讯作者：
Jones GE
影响因子：
2.6
作者：
AlKhater, Suzan A.
通讯作者：
AlKhater, Suzan A.
影响因子：
8.8
作者：
Ferrero, Giuliano;Mahony, Christopher B.;Wittamer, Valerie
通讯作者：
Wittamer, Valerie