Role for ETS domain transcription factors Pea3/Erm in mouse lung development

摘要

Duringthedevelopmentofthemouselung,theexpressionofanumberofgenes,includingthoseencodinggrowthfactorsandcomponentsoftheirdownstreamsignalingpathways,isenrichedintheepitheliumand/ormesenchymeofthedistalbuds.Inthislocation,theyregulateprocessessuchascellproliferation,branchingmorphogenesis,andthedifferentiationofspecializedcelltypes.Here,wereportthattheexpressionofemPea3/emandemErm/em(oremEtv5,Etsvariantgene5/em),whichencodePea3subfamilyETSdomaintranscriptionfactors,isinitiallyrestrictedtothedistalbudsofthedevelopingmouselung.emErm/emistranscribedexclusivelyintheepithelium,whileemPea3/emisexpressedinbothepitheliumandmesenchyme.emErm/Pea3/emaredownstreamofFGFsignalingfromthemesenchyme,buttheirresponsestowarddifferentFGFsarenotthesame.ThefunctionsofthetwoproteinswereinvestigatedbytransgenicexpressionofarepressorformofErmspecificallyintheembryoniclungepithelium.WhenexaminedatE18.5,thedistalepitheliumoftransgeniclungsiscomposedpredominantlyofimmaturetypeIIcells,whilenomaturetypeIcellsareobserved.Incontrast,thedifferentiationofproximalepithelialcells,includingciliatedcellsandClaracells,appearstobeunaffected.AmodelisproposedfortheroleofPea3/Ermduringthedynamicprocessoflungbudoutgrowthandproximalndash;distaldifferentiation,inresponsetoFGFsignaling.OurresultsprovidethefirstfunctionalevidencethatPea3subfamilymembersplayaroleinepithelialndash;mesenchymalinteractionsduringlungorganogenesis./p/div