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 roleProgrammed Cell Death of Developing Mammalian Neurons after Genetic Deletion of Caspases
Oppenheim R, Flavell R, Vinsant S, Prevette D, Kuan C, Rakic P. Programmed Cell Death of Developing Mammalian Neurons after Genetic Deletion of Caspases. Journal Of Neuroscience 2001, 21: 4752-4760. PMID: 11425902, PMCID: PMC6762357, DOI: 10.1523/jneurosci.21-13-04752.2001.Peer-Reviewed Original ResearchConceptsCell deathGenetic deletionExtensive cytoplasmic vacuolizationPro-apoptotic proteasesCaspase familySpecific caspasesChromatin condensationNonapoptotic pathwaysPostmitotic neuronsCaspase-9Mammalian neuronsCell typesDeath processSpecific perturbationsCaspase-3Altered morphologyCaspasesNuclear changesKey membersDeletionUTP nickCytoplasmic vacuolizationElectron microscopic levelTerminal deoxynucleotidyl transferase-mediated biotinylated UTP nickNeuronal populationsBcl-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
Mechanisms of programmed cell death in the developing brain
Kuan C, Roth K, Flavell R, Rakic P, Kuan C, Roth K, Flavell R, Rakic P. Mechanisms of programmed cell death in the developing brain. Trends In Neurosciences 2000, 23: 291-297. PMID: 10856938, DOI: 10.1016/s0166-2236(00)01581-2.Peer-Reviewed Original ResearchConceptsCell deathNematode Caenorhabditis elegansEarly embryonic developmentGene-targeting studiesCell death pathwaysVertebrate nervous systemMammalian brain developmentCaenorhabditis elegansEmbryonic developmentGenetic analysisPostmitotic neuronsBrain developmentNeural cell deathAnalogous functionsDistinct rolesProgenitor cellsMammalian brainApoptosisNew insightsImportant mechanismElegansHomologLater stagesNervous systemMechanismRadial Unit Hypothesis of Neocortical Expansion
Rakic P. Radial Unit Hypothesis of Neocortical Expansion. Novartis Foundation Symposia 2000, 228: 30-45. PMID: 10929315, DOI: 10.1002/0470846631.ch3.Peer-Reviewed Original ResearchConceptsRadial unit hypothesisSpecies-specific sizeFamily of genesMutations of genesVentricular zoneMammalian evolutionFounder cellsNatural selectionRegulatory genesCell divisionMorphoregulatory moleculesPostmitotic cellsTransgenic animalsCortical plateCell deathNeocortical expansionGenesBasic organizationGlial scaffoldingColumnar unitsCortical cellsCerebral cortexCellsCortical developmentSynaptic connectionsAmyloid 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-3Programmed Cell Death in Mouse Brain Development
Kuan C, Flavell R, Rakic P. Programmed Cell Death in Mouse Brain Development. Results And Problems In Cell Differentiation 2000, 30: 145-162. PMID: 10857188, DOI: 10.1007/978-3-540-48002-0_6.Peer-Reviewed Original ResearchConceptsCell death machineryMouse brain developmentCell deathDeath machineryNematode Caenorhabditis elegansBasic cellular eventsIdeal experimental systemVertebrate nervous systemBrain developmentCaenorhabditis elegansNormal human brain developmentNerve growth factorGenetic pathwaysTrophic theoryRecent geneSpecific genesCellular eventsGenetic studiesNeural developmentHuman brain developmentTargeted disruptionHigher primatesMechanistic understandingEssential roleGenesCaspase‐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 ResearchConceptsCell 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
Organotypic slice cultures for analysis of proliferation, cell death, and migration in the embryonic neocortex1Published on the World Wide Web on 8 July 1999.1
Haydar T, Bambrick L, Krueger B, Rakic P. Organotypic slice cultures for analysis of proliferation, cell death, and migration in the embryonic neocortex1Published on the World Wide Web on 8 July 1999.1. Brain Research 1999, 4: 425-437. PMID: 10592354, DOI: 10.1016/s1385-299x(99)00033-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBromodeoxyuridineCell DivisionCell MovementCell SurvivalFemaleFetusFluorescent Antibody TechniqueGlial Fibrillary Acidic ProteinIn Situ Nick-End LabelingMiceMice, Inbred ICRMicroscopy, ConfocalMicrotubule-Associated ProteinsNeocortexNeurogliaNeuronsOrgan Culture TechniquesPregnancyConceptsCell deathProper cortical developmentCell-cell interactionsDynamic cellular interactionsQuantitative confocal microscopyDiffusible regulatorsPrimary cell culturesAnalysis of proliferationCellular interactionsCellular mechanismsCortical neurogenesisNeuronal migrationConfocal microscopyCell proliferationNeocortical neurogenesisExperimental manipulationThree-dimensional environmentVivo processesCell culturesNeurogenesisPhysiological methodsTropic supportOrganotypic slice culturesProliferationCortical developmentThe 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 dysregulationFamilyKinaseDevelopment of glomerular synaptic complexes and immunohistochemical differentiation in the superficial dorsal horn of the embryonic primate spinal cord
Knyihar-Csillik E, Rakic P, Csillik B. Development of glomerular synaptic complexes and immunohistochemical differentiation in the superficial dorsal horn of the embryonic primate spinal cord. Brain Structure And Function 1999, 199: 125-148. PMID: 9930620, DOI: 10.1007/s004290050215.Peer-Reviewed Original ResearchConceptsSuperficial dorsal hornGlomerular synaptic complexesPrimate spinal cordDorsal hornDorsal root afferentsDorsal root axonsSubstance PSpinal cordSynaptic contactsPrimate dorsal hornSubstantia gelatinosa cellsPrimary afferent terminalsCB-immunoreactive cellsMacaque spinal cordFinal target cellPost-synaptic specializationsCharacteristic cytological featuresGrowth conesPre-embedding immunohistochemistryLaminae IAfferent terminalsImmunohistochemical differentiationGlomerular synapsesAxon terminalsCalcitonin gene
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
1995
Structure of the embryonic primate spinal cord at the closure of the first reflex arc
Knyihar-Csillik E, Csillik B, Rakic P. Structure of the embryonic primate spinal cord at the closure of the first reflex arc. Brain Structure And Function 1995, 191: 519-540. PMID: 7677259, DOI: 10.1007/bf00186742.Peer-Reviewed Original ResearchConceptsPrimate spinal cordReflex arcSpinal cordSpinal reflex arcAlar plateDay gestation periodAssociation interneuronsProximal dendritesAxon collateralsMotoneuronal somataFirst synapsesNeuronal perikaryaGlial cellsAfferent impulsesNumerous synapsesGolgi impregnationAssociation fibersBasal plateAxonal pathwaysAssociation neuronsCordNerve impulsesTarget cellsSynapsesCellular mechanisms