Specific Transforming Growth Factor-β Subtypes Regulate Embryonic Mouse Meckel's Cartilage and Tooth Development

摘要

Membersofthetransforminggrowthfactor-β(TGF-β)superfamilyhaveemergedascriticalregulatorsforcellgrowthanddifferentiation.WhereasthedifferentTGF-βsubtypesareequipotentinthemajorityofbiologicalassaysusingcelllinesculturedeminvitro/em,thereareindicationsthatinmorecomplexsystemsinvolvingepithelial-mesenchymalinteractions,theTGF-βsubtypesdifferintheirbiologicalactivities.TotestthehypothesisthatTGF-βsubtypesspecificallyregulateeitherMeckel'scartilageortoothmorphogenesis,wedesignedexperimentstocomparelossoffunctioneffectsofTGF-β1,TGF-β2,andTGF-β3subtypesusingaserumless,chemicallydefinedmediumtocultureembryonicmouseE10(42-44somitepairs)mandibularexplants.ThemajoreffectoflossoffunctionresultingfromabrogationofTGF-β1usingantisensetreatmentresultedina20%increase(P0.05)inchondrocytenumber,adecreaseinextracellularmatrix,anddysmorphologyoftherostralregionofMeckel'scartilage.ExogenousTGF-β1providedindistinguishablerecoverytothenormalphenotype.TGF-β2antisensetreatmentproducedathreefoldenlargement(emP/em0.05)oftoothorgansandadvancedtheirdevelopmenttothecapstage.TGF-β2providedrecoverytothenormalphenotype(e.g.,reducedtoothsizeanddevelopmenttothebudstage),whereasTGF-β1orTGF-β3polypeptideshadnoeffect.TGF-β3antisensetreatmentresultedinareductionofapproximately15%inthelengthofMeckel'scartilage.WeinterprettheseresultstosuggestthatTGF-β1functionstoregulatethenumberofchondrogeniccells,theamountofextracellularmatrix,andtherateofdevelopmentalassemblyoftherostraltoposteriorsegmentsinformingMeckel'scartilage.TGF-β2appearstoregulatetoothsizeandstageofdevelopmentwithoutaffectingcartilage.TGF-β3appearstoregulateMeckel'scartilagesizewithoutalteringtoothsizeorshape.TheresultsarediscussedintermsoftheregulatoryfunctionsoftheTGF-βsubtypesduringembryoniccraniofacialmorphogenesis./p/div