RFX2 is essential in the ciliated organ of asymmetry and an RFX2 transgene identifies a population of ciliated cells sufficient for fluid flow

摘要

Motileciliacreateasymmetricfluidflowintheevolutionarilyconservedciliatedorganofasymmetry(COA)andplayafundamentalroleinestablishingtheleftndash;right(LR)axisinvertebrateembryos.Thetranscriptionalcontrolofthelargegroupofgenesthatencodeproteinsthatcontributetociliarystructureandfunctionremainspoorlyunderstood.InthisstudywefindthatthewingedhelixtranscriptionfactorRfx2isexpressedinmotileciliainmouseandzebrafishembryos.MorpholinoknockdownofRfx2functioninthewholeembryoorspecificallyincellsofthezebrafishCOA(Kupffer'sVesicle,KV)leadstoreducedKVcilialengthandperturbationsinLRasymmetry.LRpatterningdefectsincluderandomizationoftheearlyasymmetricNodalsignalingpathwaygenesemsouthpaw/em,emlefty1/emandemlefty2/emandsubsequentreversalsintheorganprimordiaoftheheartandgut.Rfx2isalsorequiredforciliogenesisinzebrafishpronephricduct.WefurthershowthatbyrestoringLeftndash;Rightdynein(LRD)expressionandmotilityspecificallyinasubsetofciliatedcellsofthemouseCOA(posteriornotochord,PNC),wecanrestorefluidflow,asymmetricexpressionofemPitx2/emandpartiallyrescuesitusdefects./p/div