2016
Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration
Lin TV, Hsieh L, Kimura T, Malone TJ, Bordey A. Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 11330-11335. PMID: 27647922, PMCID: PMC5056085, DOI: 10.1073/pnas.1605740113.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCell Cycle ProteinsDendritic SpinesEukaryotic Initiation FactorsExcitatory Postsynaptic PotentialsGene Knockdown TechniquesGreen Fluorescent ProteinsMatrix Attachment Region Binding ProteinsMechanistic Target of Rapamycin Complex 1MiceNeurogliaNeuronsPhosphoproteinsProtein BiosynthesisRas Homolog Enriched in Brain ProteinRNA CapsRNA, Small InterferingSignal TransductionTOR Serine-Threonine KinasesTranscription FactorsConceptsBrain cytoarchitectureUpper layer cortical neuronsHyperactive mammalian targetDendritic hypertrophyCortical neuronsCap-dependent translationEctopic placementRadial gliaMammalian targetLate corticogenesisTranslational repressor eukaryotic initiation factor 4EEukaryotic initiation factor 4ENeurodevelopmental disordersProtein 1Rapamycin complex 1Molecular hallmarksInitiation factor 4EMechanisms downstreamCytoarchitectureMolecular identityMisplacementActive mutantHypertrophyGliaOveractivation
2014
FMRP S499 Is Phosphorylated Independent of mTORC1-S6K1 Activity
Bartley CM, O’Keefe R, Bordey A. FMRP S499 Is Phosphorylated Independent of mTORC1-S6K1 Activity. PLOS ONE 2014, 9: e96956. PMID: 24806451, PMCID: PMC4013076, DOI: 10.1371/journal.pone.0096956.Peer-Reviewed Original ResearchChapter 15 mTOR Signaling in Cortical Network Development
Lin T, Bordey A. Chapter 15 mTOR Signaling in Cortical Network Development. 2014, 193-205. DOI: 10.1016/b978-0-12-415804-7.00015-0.ChaptersCortical developmentCortical network developmentHyperactive mammalian targetModel disease statesCognitive dysfunctionPsychiatric disordersUtero electroporationMammalian targetNeurodegenerative diseasesMTOR signalingDisease statesCortical networksMTOR associationMTORDevelopmental aberrationsAssociationDysfunctionSeizuresMalformationsCortexDiseaseSchizophrenia
2013
mTORC1 Targets the Translational Repressor 4E-BP2, but Not S6 Kinase 1/2, to Regulate Neural Stem Cell Self-Renewal In Vivo
Hartman NW, Lin TV, Zhang L, Paquelet GE, Feliciano DM, Bordey A. mTORC1 Targets the Translational Repressor 4E-BP2, but Not S6 Kinase 1/2, to Regulate Neural Stem Cell Self-Renewal In Vivo. Cell Reports 2013, 5: 433-444. PMID: 24139800, DOI: 10.1016/j.celrep.2013.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCell Cycle ProteinsCell DifferentiationCells, CulturedEukaryotic Initiation FactorsMechanistic Target of Rapamycin Complex 1MiceMonomeric GTP-Binding ProteinsMultiprotein ComplexesNeural Stem CellsNeuropeptidesPhosphoproteinsPhosphorylationRas Homolog Enriched in Brain ProteinRibosomal Protein S6 Kinases, 90-kDaRNA InterferenceRNA, Small InterferingSirolimusTOR Serine-Threonine KinasesConceptsCap-dependent translationNeural stem cellsNSC differentiationStem Cell Self-RenewalTranslational repressor 4E-BP1P70 S6 kinase 1Neural Stem Cell Self-RenewalCell Self-RenewalRapamycin complex 1Neonatal neural stem cellsS6 kinase 1Downstream regulatory mechanismsLineage expansionSelf-RenewalRegulatory mechanismsKinase 1Kinase 1/2Constitutive activationMammalian targetCell growthStem cellsBrain sizeDifferentiationKnockdownNeuron productionRheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-Sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons
Lafourcade CA, Lin TV, Feliciano DM, Zhang L, Hsieh LS, Bordey A. Rheb Activation in Subventricular Zone Progenitors Leads to Heterotopia, Ectopic Neuronal Differentiation, and Rapamycin-Sensitive Olfactory Micronodules and Dendrite Hypertrophy of Newborn Neurons. Journal Of Neuroscience 2013, 33: 2419-2431. PMID: 23392671, PMCID: PMC3711634, DOI: 10.1523/jneurosci.1840-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell DifferentiationCell EnlargementCell Line, TumorCell MovementCerebral VentriclesDendritesElectroporationFemaleHypertrophyMaleMiceMonomeric GTP-Binding ProteinsNeural Stem CellsNeurogenesisNeuronsNeuropeptidesOlfactory BulbRas Homolog Enriched in Brain ProteinSirolimusStem CellsTOR Serine-Threonine KinasesConceptsNeural progenitor cellsWild-type miceOlfactory bulbMTOR activitySynaptic inputsEctopic neuronal differentiationSubventricular zone neural progenitor cellsActive ras homologNeuronal differentiationGABAergic synaptic inputsTsc1 mutant miceSubventricular zone progenitorsDendritic complexityNewborn neuronsTuberous sclerosisOlig2 cellsHyperactive mTORHeterozygote miceCircuit formationAction potentialsNeuronal morphologyNewborn cellsMutant miceEctopic cellsMammalian targetHypoxia-inducible factor 1a is a Tsc1-regulated survival factor in newborn neurons in tuberous sclerosis complex
Feliciano DM, Zhang S, Quon JL, Bordey A. Hypoxia-inducible factor 1a is a Tsc1-regulated survival factor in newborn neurons in tuberous sclerosis complex. Human Molecular Genetics 2013, 22: 1725-1734. PMID: 23349360, PMCID: PMC3613161, DOI: 10.1093/hmg/ddt018.Peer-Reviewed Original ResearchConceptsHypoxia-inducible factor 1aTuberous sclerosis complexShort hairpin RNANewborn neuronsFactor 1ASubventricular zoneSVZ stem cellsNewborn neuron survivalNeurogenic subventricular zoneSingle-cell electroporationTranscriptional activityShRNA expressionHairpin RNAMammalian targetMolecular determinantsNovel microenvironmentNeuron deathNeuron survivalOlfactory lesionsNeonatal miceBrain lesionsStem cellsMouse modelNeuron productionSurvival advantage
2011
Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice
Feliciano DM, Su T, Lopez J, Platel JC, Bordey A. Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice. Journal Of Clinical Investigation 2011, 121: 1596-1607. PMID: 21403402, PMCID: PMC3069783, DOI: 10.1172/jci44909.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesBase SequenceCell SizeCerebral CortexDisease Models, AnimalDNA PrimersFemaleGene Knockout TechniquesMiceMice, 129 StrainMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, Mutant StrainsMice, TransgenicPregnancySeizuresTOR Serine-Threonine KinasesTuberous SclerosisTuberous Sclerosis Complex 1 ProteinTumor Suppressor ProteinsConceptsTuberous sclerosis complexSeizure thresholdNeuronal populationsSigns of gliosisLower seizure thresholdContribution of astrocytesDiscrete neuronal populationsAutosomal dominant disorderHeterotopic nodulesCortical hyperexcitabilityCortical tubersCortical lesionsGlial reactivityIntractable seizuresCortical malformationsSoma sizeAnimal modelsTSC1 gene productAffected neuronsDendritic treeGiant cellsUtero electroporationMutant miceLesion formationMammalian target