No turning,a Mouse Mutation Causing Left–Right and Axial Patterning Defects

摘要

Patterningalongtheleft/rightaxeshelpsestablishtheorientationofvisceralorganasymmetries,aprocesswhichisoffundamentalimportancetotheviabilityofanorganism.Alinkagebetweenleft/rightandaxialpatterningisindicatedbythefindingthatanumberofgenesinvolvedinleft/rightpatterningalsoplayaroleinanteroposterioranddorsoventralpatterning.Wehaverecoveredaspontaneousmousemutationcausingleft/rightpatterningdefectstogetherwithdefectsinanteroposterioranddorsoventralpatterning.Thismutationisrecessivelethalandwasnamedemnoturning(nt)/embecausethemutantembryosfailtoundergoembryonicturning.emnt/emembryosexhibitcranialneuraltubeclosuredefectsandmalformedsomitesandarecaudallytruncated.Developmentoftheheartarrestsattheloopedhearttubestage,withcardiovasculardefectsindicatedbyballooningofthepericardialsacandthepoolingofbloodinvariousregionsoftheembryo.Interestingly,inemnt/emembryos,thedirectionofheartloopingwasrandomized.emNodal/emandemlefty,/emtwogenesthatarenormallyexpressedonlyintheleftlateralplatemesoderm,showexpressionintherightandleftlateralplatemesoderm.emLefty,/emwhichisnormallyalsoexpressedinthefloorplate,isnotfoundintheprospectivefloorplateofemnt/emembryos.Thissuggeststhepossibilityofnotochordaldefects.Thiswasconfirmedbyhistologicalanalysisandtheexaminationofemsonichedgehog,Brachyury,/emandemHNF-3β/emgeneexpression.Thesestudiesshowedthatthenotochordispresentintheearlyemnt/emembryo,butdegeneratesasdevelopmentprogresses.Overall,thesefindingssupportthehypothesisthatthenotochordplaysanactiveroleinleft/rightpatterning.Ourresultssuggestthatemnt/emmayparticipateinthisprocessbymodulatingthenotochordalexpressionofemHNF-3/emβ./p/div