Blocking Endogenous FGF-2 Activity Prevents Cranial Osteogenesis
[摘要] Normalgrowthandmorphogenesisofthecranialvaultreflectabalancebetweencellproliferationinthesuturesandosteogenesisatthemarginsofthecranialbones.Intheclinicalconditioncraniosynostosis,thesuturesfuseprematurelyasaresultofprecociousosteogenicdifferentiationandcraniofacialmalformationresults.Mutationsinseveralfibroblastgrowthfactorreceptor(FGFR)geneshavenowbeenidentifiedasbeingresponsibleforthemajorcraniosynostoticsyndromes.WehaveusedagraftingtechniquetomanipulatethelevelsofendogenousFGF-2ligandinembryonicchickcranialvaultsandtherebyperturbmorphogenesis.ImplantationofbeadsloadedwithFGF-2didnotaffectnormalcranialdevelopmentatphysiologicalconcentrations,althoughtheyelicitedamorphogeneticresponseinthelimb.ImplantationofbeadsloadedwithaneutralisingantibodytoFGF-2generatedaconcentration-dependentresponse.Whenasinglebeadwasimplanted,thegraftsgrewtoamassivesizeasaresultofincreasedcelldivisioninthetissue.WithgreaterinactivationofFGF-2protein(twotothreebeadsimplanted),allfurtherbonedifferentiationandcellproliferationwasblocked.ThesedatafurthersupporttheemergingideathattheintensityofFGF-mediatedsignallingdeterminesthedevelopmentalfateoftheskeletogeniccellsinthecranialvault.Highandlowlevelscorrelatewithdifferentiationandproliferation,respectively.Abalancebetweenthetwoensuresnormalcranialvaultmorphogenesis.ThisisconsistentwiththeobservationthatseveralFGFRmutationscausingcraniosynostosisresultinconstitutiveactivationofthereceptor.
[发布日期] [发布机构]
[效力级别] [学科分类] 生物科学（综合）
[关键词] neural crest;osteogenesis;FGF-2;cranium;suture [时效性]
