FGF-2 Deficiency Does Not Influence FGF Ligand and Receptor Expression during Development of the Nigrostriatal System 英文参考文献.docVIP

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FGF-2 Deficiency Does Not Influence FGF Ligand and Receptor Expression during Development of the Nigrostriatal System 英文参考文献.doc

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FGF-2 Deficiency Does Not Influence FGF Ligand and Receptor Expression during Development of the Nigrostriatal System 英文参考文献

FGF-2DeficiencyDoesNotInfluenceFGFLigandand ReceptorExpressionduringDevelopmentofthe NigrostriatalSystem AndreasRatzka1,OlgaBaron1,2,ClaudiaGrothe1,2 * 1InstituteofNeuroanatomy,HannoverMedicalSchool,Hannover,Germany,2CenterforSystemsNeuroscience(ZSN),Hannover,Germany Abstract Secretedproteinsofthefibroblastgrowthfactor(FGF)familyplayimportantrolesduringdevelopmentofvariousorgan systems. A detailed knowledge of their temporal and spatial expression profiles, especially of closely related FGF family members, are essential to further identification of specific functions in distinct tissues. In the central nervous system dopaminergicneuronsofthesubstantianigraandtheiraxonalprojectionsintothestriatumprogressivelydegeneratein Parkinson’sdisease.Incontrast,FGF-2deficientmicedisplayincreasednumbersofdopaminergicneurons.Inthisstudy,we determinedtheexpressionprofilesofall22FGF-ligandsand10FGF-receptorisoforms,inordertoclarify,ifFGF-2deficiency leadstocompensatoryup-regulationofotherFGFsinthenigrostriatalsystem.Threetissues,ventralmesencephalon(VM), striatum(STR)andasreferencetissuespinalcord(SC)ofwild-typeandFGF-2deficientmiceatfourdevelopmentalstages E14.5,P0,P28,andadultwerecomparativelyanalyzedbyquantitativeRT-PCR.Asnodifferencesbetweenthegenotypes wereobserved,acompensatoryup-regulationcanbeexcluded.Moreover,thisanalysisrevealedthatthemajorityofFGF- ligands (18/22) and FGF-receptors (9/10) are expressed during normal development of the nigrostriatal system and identified dynamic changes for some family members. By comparing relative expression level changes to SC reference tissue,generalalterationsinall3tissues,suchasincreasedexpressionofFGF-1,-2,-22,FgfR-2c,-3canddecreasedexpression of FGF-13 during postnatal development were identified. Further, specific changes affecting only one tissue, such as increasedFGF-16(STR)ordecreasedFGF-17(VM)expression,ortwotissues,suchasdecreasedexpressionofFGF-8(VM,STR) and FGF-15 (SC, VM) were found. Moreover, 3 developmentally down-reg