In many lower animals,germ cell formation,migration,and maintenance depend on maternally provided determinants in germ plasm.In zebrafish,these processes have been extensively studied in terms of RNA-binding proteins ...In many lower animals,germ cell formation,migration,and maintenance depend on maternally provided determinants in germ plasm.In zebrafish,these processes have been extensively studied in terms of RNA-binding proteins and other coding genes.The role of small non-coding RNAs in the regulation of primordial germ cell(PGC)development remains largely unknown and poorly investigated,even though growing interests for the importance of miRNAs involved in a wide variety of biological processes.Here,we reported the role and mechanism of the germ plasm-specific miRNA miR-202-5p in PGC migration:(i)both maternal loss and knockdown of miR-202-5p impaired PGC migration indicated by the mislocalization and reduced number of PGCs;(ii)cdc42se1 was a direct target gene of miR-202-5p,and overexpression of Cdc42se1 in PGCs caused PGC migration defects similar to those observed in loss of miR-202-5p mutants;(iii)Cdc42se1 not only interacted with Cdc42 but also inhibited cdc42 transcription,and overexpression of Cdc42 could rescue PGC migration defects in Cdc42se1 overexpressed embryos.Thus,miR-202-5p regulates PGC migration by directly targeting and repressing Cdc42se1 to protect the expression of Cdc42,which interacts with actin to direct PGC migration.展开更多
基金supported by the National Natural Science Foundation of China(31771587 and 31970535)Fundamental Research Funds for the Central Universities(17lgpy66)+2 种基金the Pearl River S&T Nova Program of Guangzhou(201806010047)the Scince and Technology Planning Project of Guangdong Province(2017A030303010)the Guangdong Natural Science Foundation(2015A030308012).
文摘In many lower animals,germ cell formation,migration,and maintenance depend on maternally provided determinants in germ plasm.In zebrafish,these processes have been extensively studied in terms of RNA-binding proteins and other coding genes.The role of small non-coding RNAs in the regulation of primordial germ cell(PGC)development remains largely unknown and poorly investigated,even though growing interests for the importance of miRNAs involved in a wide variety of biological processes.Here,we reported the role and mechanism of the germ plasm-specific miRNA miR-202-5p in PGC migration:(i)both maternal loss and knockdown of miR-202-5p impaired PGC migration indicated by the mislocalization and reduced number of PGCs;(ii)cdc42se1 was a direct target gene of miR-202-5p,and overexpression of Cdc42se1 in PGCs caused PGC migration defects similar to those observed in loss of miR-202-5p mutants;(iii)Cdc42se1 not only interacted with Cdc42 but also inhibited cdc42 transcription,and overexpression of Cdc42 could rescue PGC migration defects in Cdc42se1 overexpressed embryos.Thus,miR-202-5p regulates PGC migration by directly targeting and repressing Cdc42se1 to protect the expression of Cdc42,which interacts with actin to direct PGC migration.