Egr3 Dependent Sympathetic Target Tissue Innervation in the Absence of Neuron Death 英文参考文献.docVIP

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Egr3 Dependent Sympathetic Target Tissue Innervation in the Absence of Neuron Death 英文参考文献.doc

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Egr3 Dependent Sympathetic Target Tissue Innervation in the Absence of Neuron Death 英文参考文献

Egr3DependentSympatheticTargetTissueInnervation intheAbsenceofNeuronDeath LinLi1,LaurieC.Eldredge1,DavidH.Quach1,AvinashHonasoge1,KatherineGruner1,WarrenG. Tourtellotte1,2,3 * 1DepartmentofPathology,FeinbergSchoolofMedicine,NorthwesternUniversity,Chicago,Illinois,UnitedStatesofAmerica,2DivisionofNeuropathology,Department ofPathology,FeinbergSchoolofMedicine,NorthwesternUniversity,Chicago,Illinois,UnitedStatesofAmerica,3DepartmentofNeurology,FeinbergSchoolofMedicine, NorthwesternUniversity,Chicago,Illinois,UnitedStatesofAmerica Abstract Nerve Growth Factor (NGF) is atarget tissue derived neurotrophin required for normal sympathetic neuron survival and targettissueinnervation.NGFsignalingregulatesgeneexpressioninsympatheticneurons,whichinturnmediatescritical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS) development.Egr3isatranscriptionfactorregulatedbyNGFsignalinginsympatheticneuronsthatisessentialfornormal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neurondeathandabnormalinnervationtomanytargettissues.Theextenttowhichsympatheticinnervationabnormalities intheabsenceofEgr3iscausedbyalteredinnervationorbyneurondeathduringdevelopmentisunknown.UsingBax- deficientmicetoabrogateapoptoticsympatheticneurondeathinvivo,weshowthatEgr3hasanessentialroleintarget tissueinnervationintheabsenceofneurondeath.Sympathetictargettissueinnervationisabnormalinmanytargettissues intheabsenceofneurondeath,andlikeNGF,Egr3alsoappearstoeffecttargettissueinnervationheterogeneously.Insome tissues,suchasheart,spleen,bowel,kidney,pinealglandandtheeye,Egr3isessentialfornormalinnervation,whereasin othertissuessuchaslung,stomach,pancreasandliver,Egr3appearstohavelittleroleininnervation.Moreover,insalivary glands and heart, two tissues where Egr3 has an essential role in sympathetic innervation, NGF and NT-3 are expressed normally in the absence of Egr3 indicating that