Lrrn1 is required for formation of the midbrain–hindbrain boundary and organiser through regulation of affinity differences between midbrain and hindbrain cells in chick

摘要

Themidbrainndash;hindbrainboundary(MHB)actsasanorganiser/signallingcentretopatterntectalandcerebellarcompartments.Cellsinadjacentcompartmentsmustbedistinctfromeachotherforboundaryformationtooccurattheinterface.Herewehaveidentifiedtheleucine-richrepeat(LRR)neuronal1(Lrrn1)proteinasakeyregulatorofthisprocessinchick.TheLrrnfamilyisorthologoustotheemDrosophila/emtartan/capricious(trn/caps)family.Differentialexpressionoftrn/capspromotesanaffinitydifferenceandboundaryformationbetweenadjacentcompartmentsinanumberofcontexts;forexample,inthewing,legandeyeimaginaldiscs.HereweshowthatemLrrn1/emisexpressedinmidbraincellsbutnotinanteriorhindbraincells.emLrrn1/emisdown-regulatedintheanteriorhindbrainbytheorganisersignallingmoleculeFGF8,therebycreatingadifferentialaffinitybetweenthesetwocompartments.Lrrn1isrequiredfortheformationofMHBmdash;lossoffunctionleadstoalossofthemorphologicalconstrictionandlossofemFgf8/em.CellsoverexpressingemLrrn1/emviolatetheboundaryandresultinalossofcellrestrictionbetweenmidbrainandhindbraincompartments.Lrrn1alsoregulatestheglycosyltransferaseemLunaticFringe/em,amodulatorofNotchsignalling,maintainingitsexpressioninmidbraincellswhichisinstrumentalinMHBboundaryformation.Thus,Lrrn1providesalinkbetweencellaffinity/compartmentsegregation,andcellsignallingtospecifyboundarycellfate./p/div