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