Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injur...Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injury and affect axon regeneration.A previous study identified dusp2 as an upregulated gene in zebrafish with spinal cord injury.Here,we found that dual specificity phosphatase 2(DUSP2)is a negative regulator of axon regeneration of the Mauthner cell(M-cell).DUSP2 is a phosphatase that mediates the dephosphorylation of JNK.In this study,we knocked out dusp2 by CRISPR/Cas9 and found that M-cell axons of dusp2(-/-)zebrafish had a better regeneration at the early stage after birth(within 8 days after birth),while those of dusp2^(+/-)zebrafish did not.Overexpression of DUSP2 in Tg(Tol 056)zebrafish by single-cell electroporation retarded the regeneration of M-cell axons.Western blotting results showed that DUSP2 knockout slightly increased the levels of phosphorylated JNK.These findings suggest that knocking out DUSP2 promoted the regeneration of zebrafish M-cell axons,possibly through enhancing JNK phosphorylation.展开更多
Dual oxidase(duox)-deriyed reactive oxygen species(ROS)have been correlated with neuronal polarity,cerebellar development,and neuroplasticity.However,there have not been many comprehensive studies of the effect of ind...Dual oxidase(duox)-deriyed reactive oxygen species(ROS)have been correlated with neuronal polarity,cerebellar development,and neuroplasticity.However,there have not been many comprehensive studies of the effect of individual duox isoforms on central-axon regenerationin vivo.Here,we explored this question in zebrafish,an excellent model organism for central-axon regeneration studies.In our research,mutation of the duox gene with CRISPR/Cas9 significantly retarded the singleaxon regeneration of the zebrafish Mauthner cell in vivo.Using deep transcriptome sequencing,we found that the expression levels of related functional enzymes in mitochondria were down-regulated in duox mutant fish.In vivo imaging showed that duox mutants had significantly disrupted mitochondrial transport and redox state in single Mauthner-cell axon.Our research data provide insights into how duox is involved in central-axon regeneration by changing mitochondrial transport.展开更多
基金granted by the National Natural Science Foundation of China,No.82071357Ministry of Science and Technology of China,No.2019YFA0405600(both to BH).
文摘Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injury and affect axon regeneration.A previous study identified dusp2 as an upregulated gene in zebrafish with spinal cord injury.Here,we found that dual specificity phosphatase 2(DUSP2)is a negative regulator of axon regeneration of the Mauthner cell(M-cell).DUSP2 is a phosphatase that mediates the dephosphorylation of JNK.In this study,we knocked out dusp2 by CRISPR/Cas9 and found that M-cell axons of dusp2(-/-)zebrafish had a better regeneration at the early stage after birth(within 8 days after birth),while those of dusp2^(+/-)zebrafish did not.Overexpression of DUSP2 in Tg(Tol 056)zebrafish by single-cell electroporation retarded the regeneration of M-cell axons.Western blotting results showed that DUSP2 knockout slightly increased the levels of phosphorylated JNK.These findings suggest that knocking out DUSP2 promoted the regeneration of zebrafish M-cell axons,possibly through enhancing JNK phosphorylation.
基金the National Natural Science Foundation of China(31771183 and 31701027)the National Key Research and Development Program of China(2019YFA0405603 and 2019YFA0405600)。
文摘Dual oxidase(duox)-deriyed reactive oxygen species(ROS)have been correlated with neuronal polarity,cerebellar development,and neuroplasticity.However,there have not been many comprehensive studies of the effect of individual duox isoforms on central-axon regenerationin vivo.Here,we explored this question in zebrafish,an excellent model organism for central-axon regeneration studies.In our research,mutation of the duox gene with CRISPR/Cas9 significantly retarded the singleaxon regeneration of the zebrafish Mauthner cell in vivo.Using deep transcriptome sequencing,we found that the expression levels of related functional enzymes in mitochondria were down-regulated in duox mutant fish.In vivo imaging showed that duox mutants had significantly disrupted mitochondrial transport and redox state in single Mauthner-cell axon.Our research data provide insights into how duox is involved in central-axon regeneration by changing mitochondrial transport.