Vezatin, a protein associated to adherens junctions, is required for mouse blastocyst morphogenesis ☆

摘要

Cellndash;cellinteractionsplayamajorroleduringpreimplantationdevelopmentofthemouseembryo.Theformationofadherensjunctionsisamajorfeatureofcompaction,thefirstmorphogeneticeventthattakesplaceatthe8-cellstage.Then,duringthefollowingtwocellcycles,tightjunctionsform,andtheouterlayerofcellsdifferentiateintoafunctionalepithelium,leadingtotheformationoftheblastocoelcavity.Untilnow,E-cadherinwastheonlytransmembranemoleculelocalizedinadherensjunctionsandrequiredforearlydevelopment.Vezatinisatransmembraneproteinofadherensjunctions,interactingwiththeE-cadherinndash;cateninscomplex.Here,weshowthatvezatinisexpressedveryearlyduringmousepreimplantationdevelopment.Itco-localizeswithE-cadherinthroughoutdevelopment,beingfoundallaroundthecellcortexbeforecompactionandbasolaterallyinadherensjunctionsthereafter.Inaddition,vezatinisalsodetectedinnucleiduringmostofthecellcycle.Finally,usingamorpholino-oligonucleotideapproachtoinhibitvezatinfunctionduringpreimplantationdevelopment,weobservedthatinhibitionofvezatinsynthesisleadstoacellcyclearrestwithlimitedcellndash;cellinteractions.ThisphenotypecanberescuedwhenmRNAscodingforvezatinmissingthe5prime;UTRareco-injectedwiththeanti-vezatinmorpholino-oligonucleotide.Cellsderivedfromblastomeresinjectedwithmorpholino-oligonucleotidehadareducedamountofvezatinconcomitantlywithadecreaseinthequantityofE-cadherinandβ-cateninlocalizedintheareasofintercellularcontact.ShiftinE-cadherincorticaldistributionwascorrelatedwithastrongdecreaseinE-cadherinmRNAandproteincontents.Altogether,theseobservationsdemonstratethatvezatinisrequiredformorphogenesisofthepreimplantationmouseembryo./p/div