Ectodermal FGFs Induce Perinodular Inhibition of Limb Chondrogenesis in Vitro and in Vivo via FGF Receptor 2

Developmental Biology

Sherry A Downie¹  Nadezhda Mezentseva¹  Natalie B Bronstein¹  Pamela A Maher¹  Marie Z Moftah¹  Jiayu Pu¹  Stuart A Newman¹ 

[1] Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, 10595

关键词: limb development;    pattern formation;    fibroblast growth factor;    FGF receptor;    lateral inhibition;   

DOI  :  10.1006/dbio.2002.0766

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Theformationofcartilageelementsinthedevelopingvertebratelimb,wheretheyserveasprimordiafortheappendicularskeleton,isprecededbytheappearanceofdiscretecellularcondensations.Controlofthesizeandspacingofthesecondensationsisakeyaspectofskeletalpatternformation.Limbbudcellculturesgrownintheabsenceofectodermformedcontinuoussheet-likemassesofcartilage.Withtheinclusionofectoderm,theseculturesproducedoneormorecartilagenodulessurroundedbyzonesofnoncartilaginousmesenchyme.Ectodermalfibroblastgrowthfactors(FGF2andFGF8),butnotamesodermalFGF(FGF7),substitutedforectodermininhibitingchondrogenicgeneexpression,withsomecombinationsofthetwoectodermalfactorsleadingtowell-spacedcartilagenodulesofrelativelyuniformsize.TreatmentofcultureswithSU5402,aninhibitorFGFreceptortyrosinekinaseactivity,renderedFGFsineffectiveininducingperinodularinhibition.InhibitionofproductionofFGFreceptor2(FGFR2)bytransfectionofwingandlegcellcultureswithantisenseoligodeoxynucleotidesblockedappearanceofectoderm-orFGF-inducedzonesofperinodularinhibitionofchondrogenesisand,whenintroducedintothelimbbudsofdevelopingembryos,ledtoshorter,thicker,andfusedcartilageelements.BecauseFGFR2isexpressedmainlyatsitesofprecartilagecondensationduringlimbdevelopmentinvivoandinvitro,theseresultssuggestthatactivationofFGFR2byFGFsduringdevelopmentelicitsalateralinhibitorofchondrogenesisthatlimitstheexpansionofdevelopingskeletalelements.

【 授权许可】

Unknown