Rac1 and Rac3 GTPases Regulate the Development of Hilar Mossy Cells by Affecting the Migration of Their Precursors to the Hilus 英文参考文献.docVIP

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Rac1 and Rac3 GTPases Regulate the Development of Hilar Mossy Cells by Affecting the Migration of Their Precursors to the Hilus 英文参考文献.doc

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Rac1 and Rac3 GTPases Regulate the Development of Hilar Mossy Cells by Affecting the Migration of Their Precursors to the Hilus 英文参考文献

Rac1andRac3GTPasesRegulatetheDevelopmentof HilarMossyCellsbyAffectingtheMigrationofTheir PrecursorstotheHilus RobertaPennucci,StefaniaTavano,DilettaTonoli,SaraGualdoni,IvandeCurtis* CellAdhesionUnit,DivisionofNeuroscience,SanRaffaeleScientificInstituteandSanRaffaeleUniversity,Milano,Italy Abstract We have previously shown that double deletion of the genes for Rac1 and Rac3 GTPases during neuronal development affectslatedevelopmentaleventsthatperturbthecircuitryofthehippocampus,withensuingepilepticphenotype.These effects include a defect in mossy cells, the major class of excitatory neurons of the hilus. Here, we have addressed the mechanismsthataffectthelossofhilarmossycellsinthedorsalhippocampusofmicedepletedofthetwoRacGTPases. Quantificationshowedthatthelossofmossycellswasevidentalreadyatpostnatalday8,soonafterthesecellsbecome identifiablebyaspecificmarkerinthedorsalhilus.Comparativeanalysisofthehilarregionfromcontrolanddoublemutant mice revealed that synaptogenesis was affected in the double mutants, with strongly reduced presynaptic input from dentategranulecells.Wefoundthatapoptosiswasequallylowinthehippocampusofbothcontrolanddoubleknockout mice. Labelling with bromodeoxyuridine at embryonic day 12.5 showed no evident difference in the proliferation of neuronalprecursorsinthehippocampalprimordium,whiledifferencesinthenumberofbromodeoxyuridine-labelledcells in the developing hilus revealed a defect in the migration of immature, developing mossy cells in the brain of double knockoutmice.Overall,ourdatashowthatRac1andRac3GTPasesparticipateinthenormaldevelopmentofhilarmossy cells,andindicatethattheyareinvolvedintheregulationofthemigrationofthemossycellprecursorbypreventingtheir arrivaltothedorsalhilus. Citation:PennucciR,TavanoS,TonoliD,GualdoniS,deCurtisI(2011)Rac1andRac3GTPasesRegulatetheDevelopmentofHilarMossyCellsbyAffectingthe MigrationofTheirPrecursorstotheHilus.PLoSONE6(9):e24819.doi:10.1371/journal.pone.0024819 Editor:FerdinandoDiCunto,UniversityofTurin,I