N6-methyladenosine(m6A)plays a key role in mammalian early embryonic development and cell lineage differentiation.However,the role and mechanisms of 18S ribosomal RNA(rRNA)m6A methyltransferase METTL5 in early embryon...N6-methyladenosine(m6A)plays a key role in mammalian early embryonic development and cell lineage differentiation.However,the role and mechanisms of 18S ribosomal RNA(rRNA)m6A methyltransferase METTL5 in early embryonic development remain unclear.Here,we found that 18S rRNA m6A methyltransferase METTL5 plays an important role in porcine early embryonic development.METTL5 knockdown and overexpression significantly reduced the developmental efficiency of porcine early embryos and impaired cell lineage allocation.METTL5 knockdown apparently decreased the global translation efficiency in blastocyst,while METTL5 overexpression increased the global translation efficiency.Furthermore,METTL5 knockdown did not affect the abundance of CDX2 mRNA,but resulted in a significant reduction in CDX2 protein levels.Moreover,the low developmental efficiency and abnormal lineage distribution of METTL5 knockdown embryos could be rescued by CDX2 overexpression.Collectively,our results demonstrated that 18S rRNA methyltransferase METTL5 regulates porcine early embryonic development via modulating the translation of CDX2.展开更多
The liver is a key endoderm-derived multifunctional organ within the digestive system.Prospero homeobox 1(Prox1)is an essential transcription factor for liver development,but its specific function is not well understo...The liver is a key endoderm-derived multifunctional organ within the digestive system.Prospero homeobox 1(Prox1)is an essential transcription factor for liver development,but its specific function is not well understood.Here,we show that hepatic development,including the formation of intrahepatic biliary and vascular networks,is severely disrupted in prox1a mutant zebrafish.We find that Prox1a is essential for liver growth and proper differentiation but not required for early hepatic cell fate specification.Intriguingly,prox1a depletion leads to ectopic initiation of a Cdx1b-mediated intestinal program and the formation of intestinal lumen-like structures within the liver.Morpholino knockdown of cdx1b alleviates liver defects in the prox1a mutant zebrafish.Finally,chromatin immunoprecipitation analysis reveals that Prox1a binds directly to the promoter region of cdx1b,thereby repressing its expression.Overall,our findings indicate that Prox1a is required to promote and protect hepatic development by repression of Cdx1b-mediated intestinal cell fate in zebrafish.展开更多
基金supported by grants from the Sub-project of National Key Research and Development Program of China(2021YFA0805905-1)the Special Fund for Anhui Agriculture Research System,China(AHCYJSTX-04)+2 种基金the Joint Research Project on the Anhui Local Pigs Breeding and Utilization,China(340000211260001000431)the Open Project of Key Laboratory of Embryo Development and Reproductive Regulation of Anhui Province,China(FSKFKT004)the Major Special Science And Technology Project of Anhui Province,China(202103a06020013)。
文摘N6-methyladenosine(m6A)plays a key role in mammalian early embryonic development and cell lineage differentiation.However,the role and mechanisms of 18S ribosomal RNA(rRNA)m6A methyltransferase METTL5 in early embryonic development remain unclear.Here,we found that 18S rRNA m6A methyltransferase METTL5 plays an important role in porcine early embryonic development.METTL5 knockdown and overexpression significantly reduced the developmental efficiency of porcine early embryos and impaired cell lineage allocation.METTL5 knockdown apparently decreased the global translation efficiency in blastocyst,while METTL5 overexpression increased the global translation efficiency.Furthermore,METTL5 knockdown did not affect the abundance of CDX2 mRNA,but resulted in a significant reduction in CDX2 protein levels.Moreover,the low developmental efficiency and abnormal lineage distribution of METTL5 knockdown embryos could be rescued by CDX2 overexpression.Collectively,our results demonstrated that 18S rRNA methyltransferase METTL5 regulates porcine early embryonic development via modulating the translation of CDX2.
基金partially supported by grants from the National Key Research and Development Program of China and the National Natural Science Foundation of China(2018YFA0801000,32270889,2019YFA0802800,32070824,2015CB942800,2016YFA0100500,31871458,31671500,and 81371264)supported by Beijing Natural Science Foundation(5242009)a grant from the Fisheries Innovation Team of Beijing Agriculture Innovation Consortium(BAIC07-2023-02).
文摘The liver is a key endoderm-derived multifunctional organ within the digestive system.Prospero homeobox 1(Prox1)is an essential transcription factor for liver development,but its specific function is not well understood.Here,we show that hepatic development,including the formation of intrahepatic biliary and vascular networks,is severely disrupted in prox1a mutant zebrafish.We find that Prox1a is essential for liver growth and proper differentiation but not required for early hepatic cell fate specification.Intriguingly,prox1a depletion leads to ectopic initiation of a Cdx1b-mediated intestinal program and the formation of intestinal lumen-like structures within the liver.Morpholino knockdown of cdx1b alleviates liver defects in the prox1a mutant zebrafish.Finally,chromatin immunoprecipitation analysis reveals that Prox1a binds directly to the promoter region of cdx1b,thereby repressing its expression.Overall,our findings indicate that Prox1a is required to promote and protect hepatic development by repression of Cdx1b-mediated intestinal cell fate in zebrafish.
