Sfrp1 and Sfrp2 are not involved in Wnt/β-catenin signal silencing during lens induction but are required for maintenance of Wnt/β-catenin signaling in lens epithelial cells

摘要

Duringeyelensdevelopment,regulationofWnt/β-cateninsignalingiscriticalfortwomajorprocesses:initiallyitmustbesilentinthelensplacodeforlensdevelopmenttoproceed,butsubsequentlyitisrequiredformaintenanceofthelensepithelium.ItisnotknownhowthesedifferentphasesofWnt/β-cateninactivity/inactivityareregulated.Secretedfrizzledrelatedprotein-2(Sfrp2),aputativeWnt-Fzantagonist,isexpressedinlensplacodeandinlensepithelialcellsandhasbeenputforwardasacandidateforregionalWnt/β-cateninpathwayregulation.Hereweshowitsclosely-relatedisoform,emSfrp/em1,hasacomplimentarypatternofexpressioninthelens,beingabsentfromtheplacodeandepitheliumbutexpressedinthefibers.AsmicewithsingleknockoutsofemSfrp/em1oremSfrp/em2hadnodefectsinlensformation,weexaminedlensesofemSfrp/em1andemSfrp/em2doubleknockout(DKO)miceandshowedthattheyformedlensplacodeandsubsequentlensstructures.ConsistentwiththiswedidnotobserveectopicTCF/LefactivityinlensplacodeofDKOs.ThisindicatesthatSfrp1andSfrp2individually,ortogether,donotconstitutetheputativenegativeregulatorthatblocksWnt/β-cateninsignalingduringlensinduction.Incontrast,Sfrp1andSfrp2appeartohaveapositiveregulatoryfunctionbecauseWnt/β-cateninsignalinginlensepithelialcellswasreducedinemSfrp/em1andemSfrp/em2DKOmice.LensesthatformedinDKOmiceweresmallerthancontrolsandexhibitedadeficientepithelium.ThusSfrpsplayaroleinlensdevelopment,atleastinpart,byregulatingaspectsofWnt/β-cateninsignalinginlensepithelialcells./p/div