2009
Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling
Torii M, Hashimoto-Torii K, Levitt P, Rakic P. Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling. Nature 2009, 461: 524-528. PMID: 19759535, PMCID: PMC2874978, DOI: 10.1038/nature08362.Peer-Reviewed Original ResearchConceptsNeocortical excitatory neuronsRadial glial fibersColumnar organizationEphA/ephrinCerebral cortexFunctional impairmentNeuronal clonesExcitatory neuronsGlial fibersTangential migrationCortical columnsNeural progenitorsCircuit developmentEphrinProliferative unitsPopulationClonal populationsCortexNeurons
2001
Requirement of the JIP1 scaffold protein for stress-induced JNK activation
Whitmarsh A, Kuan C, Kennedy N, Kelkar N, Haydar T, Mordes J, Appel M, Rossini A, Jones S, Flavell R, Rakic P, Davis R. Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes & Development 2001, 15: 2421-2432. PMID: 11562351, PMCID: PMC312784, DOI: 10.1101/gad.922801.Peer-Reviewed Original ResearchConceptsJIP1 scaffold proteinSignal transduction pathwaysScaffold proteinTransduction pathwaysMAP kinase signal transduction pathwayJNK activationStress-induced JNK activationKinase signal transduction pathwayC-Jun N-terminal kinase (JNK) signal transduction pathwayExposure of cellsHomologous recombinationEnvironmental stressPrimary hippocampal neuronsC-JunAnoxic stressJIP1ProteinPathwayJNKExcitotoxic stressHippocampal neuronsActivationGenesStressCritical componentJNK3 contributes to c‐Jun activation and apoptosis but not oxidative stress in nerve growth factor‐deprived sympathetic neurons
Bruckner S, Tammariello S, Kuan C, Flavell R, Rakic P, Estus S. JNK3 contributes to c‐Jun activation and apoptosis but not oxidative stress in nerve growth factor‐deprived sympathetic neurons. Journal Of Neurochemistry 2001, 78: 298-303. PMID: 11461965, DOI: 10.1046/j.1471-4159.2001.00400.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornApoptosisCells, CulturedGenes, junGenotypeIsoenzymesMiceMice, KnockoutMitogen-Activated Protein Kinase 10Mitogen-Activated Protein KinasesNerve Growth FactorNerve Tissue ProteinsNeuronsOxidative StressPhosphorylationProtein-Tyrosine KinasesProto-Oncogene Proteins c-junReverse Transcriptase Polymerase Chain ReactionSuperior Cervical GanglionConceptsJun kinaseC-Jun phosphorylationC-JunDominant negative proteinSympathetic neuronal deathProtein kinase pathwayOxidative stressC-jun inductionC-Jun activationPhosphorylated c-JunApoptotic roleJNK kinaseKinase pathwayNegative proteinJNK isoformsJNK pathwayOverall pathwayNeuronal deathSympathetic neuronsApoptosisJNK3NGF deprivationKinasePhosphorylationCritical roleBcl-XL–Caspase-9 Interactions in the Developing Nervous System: Evidence for Multiple Death Pathways
Zaidi A, D'Sa-Eipper C, Brenner J, Kuida K, Zheng T, Flavell R, Rakic P, Roth K. Bcl-XL–Caspase-9 Interactions in the Developing Nervous System: Evidence for Multiple Death Pathways. Journal Of Neuroscience 2001, 21: 169-175. PMID: 11150333, PMCID: PMC6762421, DOI: 10.1523/jneurosci.21-01-00169.2001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-2-Associated X ProteinBcl-X ProteinCaspase 3Caspase 9CaspasesCells, CulturedCytarabineGanglia, SpinalGenes, LethalHeterozygoteHomozygoteImmunohistochemistryIn Situ Nick-End LabelingLiverMiceMice, KnockoutNervous SystemNeuronsProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2TelencephalonTumor Suppressor Protein p53ConceptsGene family membersCaspase-9 deficiencyCaspase-9Telencephalic neural precursor cellsCell deathDouble homozygous mutantsCaspase family membersMultiple death pathwaysNormal nervous system developmentBcl-2Nervous system developmentBax-deficient neuronsNeuronal apoptosisTelencephalic neuronsDeficient embryosNeural precursor cellsDeath pathwaysFamily membersHomozygous mutantsApoptotic pathwayObligate pathwayBcl-xLApoptosis inducersDeficient neuronsTargeted disruption
2000
Amyloid Beta-Induced Neuronal Death is Bax-Dependent but Caspase-Independent
Selznick L, Zheng T, Flavell R, Rakic P, Roth K. Amyloid Beta-Induced Neuronal Death is Bax-Dependent but Caspase-Independent. Journal Of Neuropathology & Experimental Neurology 2000, 59: 271-279. PMID: 10759182, DOI: 10.1093/jnen/59.4.271.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid Chloromethyl KetonesAmyloid beta-PeptidesAnimalsApoptosisBcl-2-Associated X ProteinCaspase 3Caspase InhibitorsCaspasesCell DeathCells, CulturedCysteine Proteinase InhibitorsDose-Response Relationship, DrugFemaleGlycoproteinsIn Situ Nick-End LabelingMaleMiceMice, KnockoutMicrotubule-Associated ProteinsMicrotubulesNeuronsPaclitaxelProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2TelencephalonConceptsNeuronal deathNeuronal apoptosisCaspase-3 activationTelencephalic neuronsFibrillar amyloid-beta (Abeta) peptidesAbeta-induced neuronal apoptosisAD treatment strategiesAbeta-induced neuronal deathPathogenesis of ADAlzheimer's disease brainEffects of AbetaAmyloid-beta peptideApoptotic nuclear featuresUnderlying pathophysiologyTreatment strategiesDisease brainSenile plaquesNeurotoxic effectsAmyloid betaCalpain inhibitionPharmacological inhibitionBeta peptideNuclear featuresAbetaCaspase-3Caspase‐3 is required for apoptosis‐associated DNA fragmentation but not for cell death in neurons deprived of potassium
D'Mello S, Kuan C, Flavell R, Rakic P. Caspase‐3 is required for apoptosis‐associated DNA fragmentation but not for cell death in neurons deprived of potassium. Journal Of Neuroscience Research 2000, 59: 24-31. PMID: 10658182, DOI: 10.1002/(sici)1097-4547(20000101)59:1<24::aid-jnr4>3.0.co;2-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCaspase 3CaspasesCell Culture TechniquesDNA FragmentationMiceMice, KnockoutNeuronsPotassium DeficiencyConceptsCell deathCaspase-3Apoptosis-associated DNA fragmentationDNA fragmentationCell death pathwaysRegulated cell deathPan-caspase inhibitorApoptosis-inducing stimuliDeath pathwaysChromatin condensationCaspase inhibitorsCaspase inhibitionApoptotic featuresCerebellar granule neuronsPotassium deprivationFmkCultured cerebellar granule neuronsCaspasesCrucial effectorNonneuronal cellsApoptosisSame extentGranule neuronsPivotal roleNeuronal death
1999
The Jnk1 and Jnk2 Protein Kinases Are Required for Regional Specific Apoptosis during Early Brain Development
Kuan C, Yang D, Roy D, Davis R, Rakic P, Flavell R. The Jnk1 and Jnk2 Protein Kinases Are Required for Regional Specific Apoptosis during Early Brain Development. Neuron 1999, 22: 667-676. PMID: 10230788, DOI: 10.1016/s0896-6273(00)80727-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBrainCalcium-Calmodulin-Dependent Protein KinasesCaspasesEmbryonic and Fetal DevelopmentEnzyme ActivationGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicJNK Mitogen-Activated Protein KinasesMiceMice, KnockoutMitogen-Activated Protein Kinase 9Mitogen-Activated Protein KinasesNervous SystemProtein KinasesRhombencephalonConceptsNeural tube closureBrain developmentEmbryonic lethalDouble mutantKinase familyCompound mutantsProtein kinaseCaspase activationPrecocious degenerationJNK2 geneTube closureEarly brain developmentCell deathJNK1Different membersSpecific apoptosisApoptosisMutantsMutant miceJNK2JNK3Mutant forebrainSevere dysregulationFamilyKinase
1998
Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9
Kuida K, Haydar T, Kuan C, Gu Y, Taya C, Karasuyama H, Su M, Rakic P, Flavell R. Reduced Apoptosis and Cytochrome c–Mediated Caspase Activation in Mice Lacking Caspase 9. Cell 1998, 94: 325-337. PMID: 9708735, DOI: 10.1016/s0092-8674(00)81476-2.Peer-Reviewed Original ResearchConceptsCritical upstream activatorUpstream activatorCaspase-9Cell death machineryCytochrome cDeath machineryApoptotic stimuliCaspase activationCaspase cascadeDNA fragmentationPrevents activationCytosolic extractsEmbryonic brainCaspasesReduced apoptosisCASP9ApoptosisActivatorCASP3Brain developmentKnockout miceEssential componentCleavageActivationVivo
1997
Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene
Yang D, Kuan C, Whitmarsh A, Rinócn M, Zheng T, Davis R, Rakic P, Flavell R. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 1997, 389: 865-870. PMID: 9349820, DOI: 10.1038/39899.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisDrug ResistanceExcitatory Amino Acid AgonistsGene ExpressionGene TargetingGlutamic AcidHippocampusKainic AcidMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 10Mitogen-Activated Protein KinasesNeuronsPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junSeizuresSignal TransductionTranscription Factor AP-1ConceptsKainic acidGlutamate receptor agonist kainic acidAgonist kainic acidExcitotoxicity-induced apoptosisExcitatory amino acidsHippocampal neuron apoptosisHippocampus of miceStress-induced neuronal apoptosisObserved neuroprotectionGlutamate neurotoxicitySeizure activityNeuron apoptosisGlutamate toxicityNeuronal apoptosisAP-1 transcription factor complexJNK3 geneMutant miceMiceMembrane depolarizationNoxious stressTranscription factor complexApoptosisC-JunRecent studiesTranscriptional activity
1996
Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice
Kuida K, Zheng T, Na S, Kuan C, Yang D, Karasuyama H, Rakic P, Flavell R. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 1996, 384: 368-372. PMID: 8934524, DOI: 10.1038/384368a0.Peer-Reviewed Original ResearchConceptsCED-3Protease familyMajor morphogenetic changesProgrammed Cell DeathICE protease familyMutant embryosCaenorhabditis elegansDeath genesMorphogenetic cellApoptotic stimuliHomologous recombinationMorphogenetic changesMendelian geneticsSequence homologyHigh similarityCell deathPremature lethalitySupernumerary cellsEmbryonic day 12Mammalian brainCPP32Critical rolePostnatal stagesApoptosisBrain development