Myofibrillogenesis in the developing zebrafish heart: A functional study of tnnt2

摘要

Varioushypotheseshavebeenproposedtoexplainthemoleculeprocessesofsarcomereassembly,partiallyduetothelackofsystematicgeneticstudiesofsarcomericgenesinaneminvivo/emmodel.Towardsthegoalofdevelopingzebrafishasavertebratemodelforthispurpose,wecharacterizedmyofibrillogenesisinadevelopingzebrafishheartandwentontoexaminethefunctionsofcardiactroponinT(tnnt2).Wefoundthatsarcomereassemblyinzebrafishheartwasinitiatedfromanon-striatedactinfilamentnetworkattheperimembraneregion,whereassarcomericmyosinisindependentlyassembledintothickfilamentsofvariablelengthbeforeintegratingintothethinfilamentnetwork.ComparedtoZ-discsthatareinitiallyalignedtoformshorterperiodicdotsandexpandedlongitudinallyatalatertime,M-linesassemblelaterandhaveaconstantlength.Depletionoffull-lengthtnnt2disruptedthestriationofthinfilamentsandZ-bodies,whichsequentiallyaffectsthestriationofthickfilamentsandM-lines.Conversely,truncationofaC-terminaltroponincomplex-bindingdomaindidnotaffectthestriationofthesesarcomeresub-structures,butresultedinreducedcardiomyocytesize.Insummary,ourdataindicatesthatzebrafishareavaluableeminvivo/emmodelforstudyingbothmyofibrillogenesisandsarcomere-basedcardiacdiseases./p/div