Blocking Endogenous FGF-2 Activity Prevents Cranial Osteogenesis

Developmental Biology

Andrew Copp¹  Peter Thorogood¹  Rachel Moore¹  Patrizia Ferretti¹ 

[1] Developmental Biology Unit, Institute of Child Health, University College London, London, WC1N 1EH, United Kingdom

关键词: neural crest;    osteogenesis;    FGF-2;    cranium;    suture;   

DOI  :  10.1006/dbio.2001.0533

学科分类：生物科学（综合）

来源: Academic Press

【 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.

【 授权许可】

Unknown