Gata5 and Gata6 are functionally redundant in zebrafish for specification of cardiomyocytes

摘要

Anoutstandingprobleminvertebratedevelopmenthasbeentodefinethegeneticprogramthatspecifiesthecardiomyocytelineage.Ithasbeenachallengetodefinethetranscriptionfactorsthatcontrolspecification,sincecandidategeneknockoutstypicallycauserathercomplexmorphogeneticdefects.Incontrast,emDrosophila/emgeneticsidentifiedsingletranscriptionfactorsthatareessentialforspecificationofcardiomyocytesfromuncommittedmesoderm.Forthosevertebrateorthologs,ithasbeenconsideredthatparalogousfamilymembersmightcompensatefortheloss-of-functionofindividualgenes.However,thishypothesishadnotbeenformallytested.Inzebrafish,defectsinemgata5/emcanleadtoalossofmyocardialtissue,butmostembryosdepletedforanysinglevertebrateGata4/5/6transcriptionfactordevelopacardiacmorphogeneticdefect,andcardiomyocytesarespecifiedanddifferentiate.Hereweshowthatinzebrafishtheemgata5/emandemgata6/emgenesareredundantforspecificationofcardiomyocytes.Embryosdepletedofthesetwogeneproductsareheartless.Restoringeithergeneproductissufficienttorescuecardiomyocytespecification.Incontrast,embryosdepletedofGata4andGata6,orGata4andGata5,developdefectivehearttubes.Ourstudyidentifiesaspecificpairofvertebratetranscriptionfactorparalogsthatisessentialforcardiomyocytespecification./p/div