Dear Editor,Lung cancer is one of the most common causes of cancerrelated deaths worldwide.Despite great progress in the development of lung cancer treatments,the prognoses of patients with advanced stage cancer remai...Dear Editor,Lung cancer is one of the most common causes of cancerrelated deaths worldwide.Despite great progress in the development of lung cancer treatments,the prognoses of patients with advanced stage cancer remains poor(Torre et al.,2015).展开更多
Background:We are using genetics to identify genes specifically involved in hearing regeneration.In a large-scale genetic screening,we identified mgat5a,a gene in the N-glycosylation biosynthesis pathway whose activit...Background:We are using genetics to identify genes specifically involved in hearing regeneration.In a large-scale genetic screening,we identified mgat5a,a gene in the N-glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration.Methods:We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish.We used pharmacological inhibition of N-glycosylation by swansonine.We also used over-expression analysis by mRNA injections to demonstrate how changes in N-glycosylation can alter cell signaling.Results:We found that mgat5a was expressed in multiple tissues during zebrafish embryo development,particularly enriched in neural tissues including the brain,retina,and lateral line neuromasts.An mgat5a insertional mutation and a CRISPR/Cas9-generated truncation mutation both caused an enhancement of hair cell regeneration which could be phenocopied by pharmacological inhibition with swansonine.In addition to hair cell regeneration,inhibition of the N-glycosylation pathway also enhanced the regeneration of lateral line axon and caudal fins.Further analysis showed that N-glycosylation altered the responsiveness of TGF-beta signaling.Conclusions:The findings from this study provide experimental evidence for the involvement of N-glycosylation in tissue regeneration and cell signaling.展开更多
基金supported by the Medical-Engineering Funding of Shanghai Jiao Tong University(ZH2018QNA20)the Shanghai Municipality Research Projects(18411966700)+3 种基金the Program for Shanghai Outstanding Medical Academic Leader,Natural Science Foundation of Shanghai,China(16ZR1437700)the Research Project for Practice Development of National TCM Clinical Research Bases(JDZX2015067)the National Natural Science Foundation of China(81904129)the Innovation Program of Shanghai Municipal Education Commission(2017-0107-00-10-E00064)。
文摘Dear Editor,Lung cancer is one of the most common causes of cancerrelated deaths worldwide.Despite great progress in the development of lung cancer treatments,the prognoses of patients with advanced stage cancer remains poor(Torre et al.,2015).
基金This research was supported by the Intramural Research Program of the National Human Genome Research Institute(ZIAHG200386-05).
文摘Background:We are using genetics to identify genes specifically involved in hearing regeneration.In a large-scale genetic screening,we identified mgat5a,a gene in the N-glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration.Methods:We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish.We used pharmacological inhibition of N-glycosylation by swansonine.We also used over-expression analysis by mRNA injections to demonstrate how changes in N-glycosylation can alter cell signaling.Results:We found that mgat5a was expressed in multiple tissues during zebrafish embryo development,particularly enriched in neural tissues including the brain,retina,and lateral line neuromasts.An mgat5a insertional mutation and a CRISPR/Cas9-generated truncation mutation both caused an enhancement of hair cell regeneration which could be phenocopied by pharmacological inhibition with swansonine.In addition to hair cell regeneration,inhibition of the N-glycosylation pathway also enhanced the regeneration of lateral line axon and caudal fins.Further analysis showed that N-glycosylation altered the responsiveness of TGF-beta signaling.Conclusions:The findings from this study provide experimental evidence for the involvement of N-glycosylation in tissue regeneration and cell signaling.
