Differential Fibroblast Growth Factor 8 (FGF8)-Mediated Autoregulation of Its Cognate Receptors, Fgfr1 and Fgfr3, in Neuronal Cell Lines 英文参考文献.docVIP

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Differential Fibroblast Growth Factor 8 (FGF8)-Mediated Autoregulation of Its Cognate Receptors, Fgfr1 and Fgfr3, in Neuronal Cell Lines 英文参考文献.doc

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Differential Fibroblast Growth Factor 8 (FGF8)-Mediated Autoregulation of Its Cognate Receptors, Fgfr1 and Fgfr3, in Neuronal Cell Lines 英文参考文献

DifferentialFibroblastGrowthFactor8(FGF8)-Mediated AutoregulationofItsCognateReceptors,Fgfr1and Fgfr3,inNeuronalCellLines NatashaN.Mott1,WilsonC.J.Chung2,Pei-SanTsai2,ToniR.Pak1* 1Department of Cell and Molecular Physiology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States of America, 2Department of IntegrativePhysiology,UniversityofColoradoatBoulder,Boulder,Colorado,UnitedStatesofAmerica Abstract Fibroblast growth factors (FGFs) mediate a vast range of CNS developmental processes including neural induction, proliferation,migration,andcellsurvival.DespitethecriticalroleofFGFsignalingfornormalCNSdevelopment,fewreports describe the mechanisms that regulate FGF receptor gene expression in the brain. We tested whether FGF8 could autoregulatetwoofitscognatereceptors,Fgfr1andFgfr3,inthreemurinecelllineswithdifferentlineages:fibroblast-derived cells(3T3cells),neuronalcellsderivedfromhippocampus(HT-22cells),andneuroendocrinecellsderivedfromhypothalamic gonadotropin-releasinghormone(GnRH)neurons(GT1-7cells).GnRHisproducedbyneuronsinthehypothalamusandis absolutelyrequiredforreproductivecompetenceinvertebrateanimals.SeverallinesofevidencestronglysuggestthatFgf8is criticalfornormaldevelopmentoftheGnRHsystem,therefore,theGT1-7cellsprovideduswithanadditionalendpoint,Gnrh geneexpressionandpromoteractivity,toassesspotentialdownstreamconsequencesofFGF8-inducedmodulationofFGF receptor levels. Results from this study suggest that the autoregulation of its cognate receptor represents a common downstream effect of FGF8. Further, we show that Fgfr1 and Fgfr3 are differentially regulated within the same cell type, implicatingthese tworeceptors in different biologicalroles. Moreover, Fgfr1 andFgfr3 aredifferentially regulated among differentcelltypes,suggestingsuchautoregulationoccursinacelltype-specificfashion.Lastly,wedemonstratethatFGF8b decreasesGnrhpromoteractivityandgeneexpression,possiblyreflectingadownstreamconsequenceofalteredFGFreceptor pop