Distinct and Overlapping Expression Patterns of Ligands for Eph-Related Receptor Tyrosine Kinases during Mouse Embryogenesis

摘要

RecentstudieshaveimplicatedEph-relatedreceptortyrosinekinasesandtheirmembrane-boundligandsinrestrictingorstimulatingthemovementofcellsandaxons.Membersoftheselargefamiliesofreceptorsandligandsfallintotwomajorbindingspecificityclasses,inwhichtheGPI-anchoredsubgroupofligandscaneachbindtoallmembersofasubgroupofreceptors,whereasthetransmembraneligandsinteractwithadistinctsubgroupofreceptors.Analysisofexpressionpatternsisthereforeimportantinordertounderstandwhichreceptorndash;ligandinteractionsoccureminvivo./emWehaveclonedmouseorthologuesoffivemembersoftheligandfamilyandanalysedindetailtheirdevelopmentalexpression,incomparisonwitheachother,andwiththereceptorspecificityclasstheycaninteractwith.WefindthatB61,AL-1/RAGS,LERK4,andELF-1,membersoftheGPI-anchoredsubgroupofligands,havebothdistinctandoverlappingaspectstotheirexpressioninearlymesoderm,somites,andbranchialarches;incomplex,dynamicpatternsinthelimb;andinspatialdomainsandspecificneuronsintheCNS.Similarly,Elk-Lisexpressedinhindbrainsegments,theroofplate,andfloorplate,whichoverlapswiththatofothertransmembraneligands,buthasdistinctexpressioninsomites.Theexpressiondomainsofligandsarecomplementarytothoseofthecorrespondingreceptorsinanumberoftissues,includingthemidbrain,hindbrain,anddifferentiatinglimbs,consistentwithpotentialrolesinrestrictingcellmovement.Inaddition,wefindthattherearesomeoverlapsinexpressionofreceptorsandligands,forexampleinsomitesandtheearlylimb.TakentogetherwithpreviousstudiesshowingthatEph-relatedreceptorsalsohavedistinctbutoverlappingexpressionpatterns,thesedataindicatethateachligandmayhavestage-andtissue-specificinteractionswithanindividualmemberormultiplemembersofthereceptorfamily./p/div