Loss of Mgat5a-mediated N-glycosylation stimulates regeneration in zebrafish
作者机构:Functional and Translation Genome BranchNational Human Genome Research Institute9000 Rockville PikeBuilding 50Room 5537BethesdaMD 20892USA Center for Genome RegulationFacultad de CienciasUniversidad de ChileCasilla 653SantiagoChile
出 版 物:《Cell Regeneration》 (细胞再生(英文))
年 卷 期:2016年第5卷第1期
页 面:22-33页
学科分类:0710[理学-生物学] 0831[工学-生物医学工程(可授工学、理学、医学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
主 题:Zebrafish CRISPR/Cas9 mgat5a N-glycosylation Regeneration
摘 要:Background:We are using genetics to identify genes specifically involved in hearing *** a large-scale genetic screening,we identified mgat5a,a gene in the N-glycosylation biosynthesis pathway whose activity negatively impacts hair cell ***:We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in *** used pharmacological inhibition of N-glycosylation by *** also used over-expression analysis by mRNA injections to demonstrate how changes in N-glycosylation can alter cell ***: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 *** 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 *** addition to hair cell regeneration,inhibition of the N-glycosylation pathway also enhanced the regeneration of lateral line axon and caudal *** analysis showed that N-glycosylation altered the responsiveness of TGF-beta ***:The findings from this study provide experimental evidence for the involvement of N-glycosylation in tissue regeneration and cell signaling.