2024
The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function
Nguyen L, Xu Y, Nair M, Bordey A. The mTOR pathway genes MTOR, Rheb, Depdc5, Pten, and Tsc1 have convergent and divergent impacts on cortical neuron development and function. ELife 2024, 12: rp91010. PMID: 38411613, PMCID: PMC10942629, DOI: 10.7554/elife.91010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainDrug Resistant EpilepsyMechanistic Target of Rapamycin Complex 1MiceNeuronsPyramidal CellsConceptsMouse medial prefrontal cortexMedial prefrontal cortexFocal malformations of cortical developmentMalformations of cortical developmentExcitatory synaptic activityExcitatory synaptic transmissionCortical neuron developmentPyramidal neuron morphologyMechanisms of hyperexcitabilityResponse to therapeutic interventionsMTORC1 signalingGene-specific mechanismsPrefrontal cortexFocal malformationsBrain somatic mutationsMTOR complex 1Membrane excitabilityBiallelic inactivationClinical manifestationsGene mutationsNetwork hyperexcitabilitySynaptic transmissionSynaptic activityIntractable epilepsyRepressor gene
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 mutantHypertrophyGliaOveractivationSwitching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice
Mahoney C, Feliciano DM, Bordey A, Hartman NW. Switching on mTORC1 induces neurogenesis but not proliferation in neural stem cells of young mice. Neuroscience Letters 2016, 614: 112-118. PMID: 26812181, DOI: 10.1016/j.neulet.2015.12.042.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationMechanistic Target of Rapamycin Complex 1Mice, TransgenicMultiprotein ComplexesNeural Stem CellsNeurogenesisTamoxifenTOR Serine-Threonine KinasesConceptsNeural stem cellsSubventricular zoneNeonatal subventricular zoneWeek old miceTuberous sclerosis complexStem cellsNewborn neuroblastsYoung miceOld miceProgressive lossYoung adultsRapamycin complex 1Mechanistic targetRecent evidenceProliferative cellsMiceHyperactive mTORC1Terminal differentiationCellsMTORC1 activationProliferationActivationMTORC1NeurogenesisHyperactivity
2015
Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo
Gong X, Zhang L, Huang T, Lin TV, Miyares L, Wen J, Hsieh L, Bordey A. Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo. Human Molecular Genetics 2015, 24: 5746-5758. PMID: 26220974, PMCID: PMC4581604, DOI: 10.1093/hmg/ddv295.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAxonsCarrier ProteinsCell Cycle ProteinsCell Growth ProcessesEukaryotic Initiation FactorsFemaleGene Expression RegulationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMaleMechanistic Target of Rapamycin Complex 1MiceMultiprotein ComplexesPhosphoproteinsRibosomal Protein S6 Kinases, 90-kDaSignal TransductionTOR Serine-Threonine KinasesConceptsAxon growthNew therapeutic optionsMultiple axon formationTherapeutic optionsHippocampal neuronsHyperactive mTORNeurological disordersUtero electroporationAxonal connectivityGSK3β activityTranslational repressor 4E-BPEukaryotic initiation factor 4EMTOR complex 1Translational targetsInitiation factor 4EHyperactive mTORC1VivoDownstream effectorsGSK3βAxon formationLong-range connectivityDominant negative mutantLithium chlorideMTORopathiesMTORC1
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 ResearchEmbryonic Cerebrospinal Fluid Nanovesicles Carry Evolutionarily Conserved Molecules and Promote Neural Stem Cell Amplification
Feliciano DM, Zhang S, Nasrallah CM, Lisgo SN, Bordey A. Embryonic Cerebrospinal Fluid Nanovesicles Carry Evolutionarily Conserved Molecules and Promote Neural Stem Cell Amplification. PLOS ONE 2014, 9: e88810. PMID: 24533152, PMCID: PMC3923048, DOI: 10.1371/journal.pone.0088810.Peer-Reviewed Original ResearchConceptsNeural stem cellsRapamycin complex 1 (mTORC1) pathwayIntracellular pathwaysStem cell amplificationInsulin-like growth factorCoordinated regulationGenetic programMicroRNA componentsExosome NanovesiclesEmbryonic CSFCell amplificationStem cellsENSCsPathwayCoordinated transferGrowth factorHuman embryosBrain developmentNanovesiclesMixed cultureAmplificationMoleculesEmbryosProteinExosomes
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 production