Activin A Promotes Neuronal Differentiation of Cerebrocortical Neural Progenitor Cells 英文参考文献.docVIP

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Activin A Promotes Neuronal Differentiation of Cerebrocortical Neural Progenitor Cells 英文参考文献.doc

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Activin A Promotes Neuronal Differentiation of Cerebrocortical Neural Progenitor Cells 英文参考文献

ActivinAPromotesNeuronalDifferentiationof CerebrocorticalNeuralProgenitorCells GriseldaRodr?′guez-Mart?′nez,AnayansiMolina-Herna′ndez,Iva′nVelasco* InstitutodeFisiolog?′aCelular-Neurociencias,UniversidadNacionalAuto′nomadeMe′xico,Me′xico,Me′xico Abstract Background: Activin A is a protein that participates principally in reproductive functions. In the adult brain, Activin is neuroprotective,butitsroleinbraindevelopmentisstillelusive. Methodology/Principal Findings: We studied if Activin A influences proliferation, differentiation or survival in rat cerebrocortical neural progenitor cells (NPC). After stimulation of NPC with Activin A, phosphorylation and nuclear translocationofSmad2/3wereinduced.InproliferatingNPC,Activinproducedasignificantdecreaseincellareaandalso adiscreteincreaseinthenumberofneuronsinthepresenceofthemitogenFibroblastGrowthFactor2.Thepercentagesof cells incorporating BrdU, or positive for the undifferentiated NPC markers Nestin and Sox2, were unchanged after incubation with Activin. In differentiating conditions, continuous treatment with Activin A significantly increased the number of neurons without affecting astroglial differentiation or causing apoptotic death. In cells cultured by extended periods,Activintreatmentproducedfurtherincreasesintheproportionofneurons,excludingprematurecellcycleexit.In clonalassays,Activinsignificantlyincreasedneuronalnumberspercolony,supportinganinstructiverole.Activin-induced neurogenesiswasdependentonactivationofitsreceptors,sinceincubationwiththetypeIreceptorinhibitorSB431542or theligand-trapFollistatinpreventedneuronaldifferentiation.Interestingly,SB431542orFollistatinbythemselvesabolished neurogenesisandincreasedastrogliogenesis,toasimilarextenttothatinducedbyBoneMorphogeneticProtein(BMP)4. Co-incubation of these Activin inhibitors with the BMP antagonist Dorsomorphin restored neuronal and astrocytic differentiationtocontrollevels. Conclusions:OurresultsshowaninstructiveneuronaleffectofActivinAincorticalNPC