The Outflow Tract of the Heart Is Recruited from a Novel Heart-Forming Field

摘要

Asclassicallydescribed,theprecardiacmesodermofthepairedheart-formingfieldsmigrateandfuseanteriomediallyintheventralmidlinetoformthefirstsegmentofthestraighthearttube.Thissegmentultimatelyformstherighttrabeculatedventricle.Additionalsegmentsareaddedtothecaudalendofthefirstinasequentialfashionfromtheposteriolateralheart-formingfieldmesoderm.Inthisstudywereportthatthefinalmajorheartsegment,whichformsthecardiacoutflowtract,doesnotfollowthispatternofembryonicdevelopment.Thecardiacoutlet,consistingoftheconusandtruncus,doesnotderivefromthepairedheart-formingfields,butoriginatesseparatelyfromapreviouslyunrecognizedsourceofmesodermlocatedanteriortotheinitialprimitivehearttubesegment.Fate-mappingresultsshowthatcellslabeledinthemesodermsurroundingtheaorticsacandanteriortotheprimitiverightventricleareincorporatedintoboththeconusandthetruncus.Conversely,ifcellsarelabeledintheexistingrightventriclenoincorporationintothecardiacoutletisobserved.Tissueexplantsmicrodissectedfromthisanteriormesodermregionarecapableofformingbeatingcardiacmuscleinvitrowhencoculturedwithexplantsoftheprimitiverightventricle.Thesefindingsestablishthepresenceofanotherheart-formingfield.Thisanteriorheart-formingfield(AHF)consistsofmesodermsurroundingtheaorticsacimmediatelyanteriortotheexistinghearttube.Thisnewconceptoftheheartoutlet'sembryonicoriginprovidesanewbasisforexplainingavarietyofgene-expressionpatternsandcardiacdefectsdescribedinbothtransgenicanimalsandhumancongenitalheartdisease.