Zebrafish Naked1 and Naked2 antagonize both canonical and non-canonical Wnt signaling

摘要

Wntsignalingcontrolsawiderangeofdevelopmentalprocessesanditsaberrantregulationcanleadtodisease.Tobetterunderstandtheregulationofthispathway,weidentifiedzebrafishhomologuesofNakedCuticle(Nkd),Nkd1andNkd2,whichhavepreviouslybeenshowntoinhibitcanonicalWnt/β-cateninsignaling.Zebrafishemnkd1/emexpressionincreasessubstantiallyafterthemid-blastulatransitioninapatternmirroringthatofactivatedcanonicalWnt/β-cateninsignaling,beingexpressedinboththeventrolateralblastodermmarginandalsointheaxialmesendoderm.Incontrast,zebrafishemnkd2/emismaternallyandubiquitouslyexpressed.OverexpressionofNkd1orNkd2asuppressedcanonicalWnt/β-cateninsignalingatmultiplestagesofearlyzebrafishdevelopmentandalsoexacerbatedthecyclopiaandaxialmesendodermconvergenceandextension(Camp;E)defectinthenon-canonicalWnt/PCPmutantemsilberblick/em(emslb/wnt11/em).Thus,Nkdsaresufficienttoantagonizebothcanonicalandnon-canonicalWntsignaling.ReducingNkdfunctionusingantisensemorpholinooligonucleotidesresultedinincreasedexpressionofcanonicalWnt/β-catenintargetgenes.Finally,reducingNkd1functioninemslb/emmutantssuppressedtheaxialmesendodermCamp;Edefect.ThesedataindicatethatzebrafishNkd1andNkd2functiontolimitbothcanonicalandnon-canonicalWntsignaling./p/div