Antagonistic Signals between BMP4 and FGF8 Define the Expression of Pitx1 and Pitx2 in Mouse Tooth-Forming Anlage

[摘要] MembersofthePitx/RIEGfamilyofhomeodomain-containingtranscriptionfactorshavebeenimplicatedinvertebrateorganogenesis.Inthisstudy,weexaminedtheexpressionandregulationofPitx1andPitx2duringmousetoothdevelopment.Pitx1expressionisdetectedinearlydevelopmentinawidespreadpattern,inbothepitheliumandmesenchyme,coveringthetooth-formingregioninthemandible,andisthenmaintainedinthedentalepitheliumfromthebudstagetothelatebellstage.Pitx2expression,ontheotherhand,isrestrictedtothedentalepitheliumthroughoutodontogenesis.Interestingly,fromE9.5toE10.5,theexpressiondomainsofPitx1andPitx2,inthedevelopingmandible,overlapwiththatofFgf8butareexclusivetothezoneofBmp4expression.BeadimplantationexperimentsdemonstratethatectopicexpressionofFgf8caninduce/maintaintheexpressionofbothPitx1andPitx2atE9.5.Incontrast,Bmp4-expressingtissuesandBMP4-soakedbeadswereabletorepressPitx1expressioninmandibularmesenchymeandPitx2expressioninthepresumptivedentalepithelium,respectively.However,theeffectsofFGF8andBMP4aretransient.ItthusappearsthattheearlyexpressionpatternsofPitx1andPitx2inthedevelopingmandibleareregulatedbytheantagonisticeffectsofFGF8andBMP4suchthatthePitx1andPitx2expressionpatternsaredefined.Theseresultsindicatethattheepithelial-derivedsignalingmoleculesareresponsiblenotonlyforrestrictingspecificgeneexpressioninthedentalmesenchyme,butalsofordefininggeneexpressioninthedentalepithelium.