Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish embryogenesis

摘要

ThetranscriptionalMediator(MED)isamultiproteincomplexthattransmitsinformationfromtranscriptionfactorstoRNApolymeraseII(PolII)toregulatetranscription.Atpresent,theroleofdistinctMEDsubunitsingeneraltranscriptionversustranscriptionstimulatedbyspecificsignalingpathwaysisunclear.Bymeansofpositionalcloning,werevealthatthezebrafishmutantemtennismatch/emisahypomorphicalleleofMed10,aconservedMEDmiddledomainsubunit.Usingmorpholinoantisenseoligonucleotides,wefurtherdemonstratethatreductionofMed10levelsledtoanenhancementoftheWntsignalingpathway,whilealsosuggestingaroleforMed10inmediatingtheNodalsignalingpathway.IncontrasttothedualrolesofMed10,reductionofMed12andMed13levels,twoMEDsubunitsintheregulatorydomain,ledtoanenhancementoftheWntsignalingpathwaybutnottheNodalpathway,whilereductionofMed15levels,aMEDsubunitinthetaildomain,suppressedtheNodalsignalingpathwaybutnottheWntsignalingpathway.Thus,Med10appearstobeauniqueMEDsubunitthatdifferentiallytransducesinformationfromdistinctsignalingpathwaysduringzebrafishembryogenesis./p/div