2012
Modeling human cortical development in vitro using induced pluripotent stem cells
Mariani J, Simonini MV, Palejev D, Tomasini L, Coppola G, Szekely AM, Horvath TL, Vaccarino FM. Modeling human cortical development in vitro using induced pluripotent stem cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 12770-12775. PMID: 22761314, PMCID: PMC3411972, DOI: 10.1073/pnas.1202944109.Peer-Reviewed Original ResearchConceptsHuman brain developmentHuman induced pluripotent stem cellsLayer-specific cortical neuronsBrain developmentHuman cerebral cortexHuman cortical developmentStem cellsPluripotent stem cellsCerebral cortexCortical neuronsCortical developmentCNS regionsRadial gliaCortical wallDorsal telencephalonEmbryonic telencephalonGene expression profilesInduced pluripotent stem cellsIntermediate progenitorsTelencephalic developmentTelencephalonExpression profilesTranscriptional programsCellsGliaImpaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice
Smith K, Williamson TL, Schwartz ML, Vaccarino FM. Impaired motor coordination and disrupted cerebellar architecture in Fgfr1 and Fgfr2 double knockout mice. Brain Research 2012, 1460: 12-24. PMID: 22578469, PMCID: PMC3361544, DOI: 10.1016/j.brainres.2012.04.002.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorHuman GFAP promoterInner granule cell layerDKO miceGranule cell numberGranule cell progenitorsRadial glial stem cellsMidline glial structuresImpaired motor coordinationCerebellar sizeGranule cell layerDouble knockout miceGlial precursor cellsGlial stem cellsCell numberGranule neuron precursorsGrowth factor receptorGABA interneuronsGranule cell migrationCerebral cortexExternal granular layerMolecular layerMotor coordinationGranule cellsKnockout mice
2010
Pyramidal Neurons Are Generated from Oligodendroglial Progenitor Cells in Adult Piriform Cortex
Guo F, Maeda Y, Ma J, Xu J, Horiuchi M, Miers L, Vaccarino F, Pleasure D. Pyramidal Neurons Are Generated from Oligodendroglial Progenitor Cells in Adult Piriform Cortex. Journal Of Neuroscience 2010, 30: 12036-12049. PMID: 20826667, PMCID: PMC2940828, DOI: 10.1523/jneurosci.1360-10.2010.Peer-Reviewed Original ResearchMeSH KeywordsAdult Stem CellsAnimalsAntigensAntineoplastic Agents, HormonalBromodeoxyuridineCell CountCell DifferentiationCerebral CortexDoublecortin Domain ProteinsDrug Administration ScheduleEye ProteinsGene Expression RegulationGreen Fluorescent ProteinsHomeodomain ProteinsMiceMice, Inbred C57BLMice, TransgenicMicrotubule-Associated ProteinsMyelin Proteolipid ProteinNerve Tissue ProteinsNeuronsNeuropeptidesOligodendrogliaPaired Box Transcription FactorsPAX6 Transcription FactorProteoglycansPyramidal CellsReceptor, Platelet-Derived Growth Factor alphaReceptors, N-Methyl-D-AspartateRepressor ProteinsSOXB1 Transcription FactorsTamoxifenTime FactorsConceptsOligodendroglial progenitor cellsPyramidal glutamatergic neuronsPiriform cortexAdult piriform cortexGlutamatergic neuronsCortical glutamatergic neuronsProgenitor cellsNeural stem cell markersCortical neuronal networksStem cell markersTranscription factor characteristicImmature neuronsCerebral cortexPyramidal neuronsCell markersCortexNeuronsCre-loxP recombination systemNeuronal networksLines of evidenceMarkersLow levelsCellsPrevious studiesDoublecortinFgfr2 Is Required for the Development of the Medial Prefrontal Cortex and Its Connections with Limbic Circuits
Stevens HE, Smith KM, Maragnoli ME, Fagel D, Borok E, Shanabrough M, Horvath TL, Vaccarino FM. Fgfr2 Is Required for the Development of the Medial Prefrontal Cortex and Its Connections with Limbic Circuits. Journal Of Neuroscience 2010, 30: 5590-5602. PMID: 20410112, PMCID: PMC2868832, DOI: 10.1523/jneurosci.5837-09.2010.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexCerebral cortexFibroblast growth factor receptorCKO miceExcitatory neuronsPrefrontal cortexCortical neuron developmentEntire cerebral cortexRadial glial cellsSpecific fibroblast growth factor receptorsGrowth factor receptorGABAergic neuronsLimbic circuitsCortical neuronsGlial cellsSubcortical stationsBed nucleusCortical developmentLimbic systemStria terminalisSynaptic terminalsSecondary decreaseNeuronal precursorsVentricular zoneNeuron development
2008
Decrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon 3 from the Fgf2 gene
Chen K, Ohkubo Y, Shin D, Doetschman T, Sanford LP, Li H, Vaccarino FM. Decrease in excitatory neurons, astrocytes and proliferating progenitors in the cerebral cortex of mice lacking exon 3 from the Fgf2 gene. BMC Neuroscience 2008, 9: 94. PMID: 18826624, PMCID: PMC2577114, DOI: 10.1186/1471-2202-9-94.Peer-Reviewed Original Research
2007
Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice
Smith K, Fagel DM, Stevens HE, Rabenstein RL, Maragnoli ME, Ohkubo Y, Picciotto MR, Schwartz ML, Vaccarino FM. Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice. Biological Psychiatry 2007, 63: 953-962. PMID: 17988653, DOI: 10.1016/j.biopsych.2007.09.020.Peer-Reviewed Original ResearchMeSH KeywordsAmphetamineAnimalsBehavior, AnimalBiogenic MonoaminesCell CountCentral Nervous System StimulantsCerebral CortexDisease Models, AnimalDopamine AgentsExploratory BehaviorFibroblast Growth Factor 1Glutamate DecarboxylaseHyperkinesisLocomotionMaleMethylphenidateMiceMice, KnockoutMotor ActivityNerve Tissue ProteinsNeural InhibitionNeuronsSignal TransductionConceptsInhibitory cortical circuitsCortical pyramidal neuronsD2 receptor antagonistGrowth factor receptor 1Spontaneous locomotor hyperactivityFibroblast growth factor receptor 1Factor receptor 1Inhibitory neuronal subtypesLocomotor hyperactivityDopamine agonistsCerebral cortexPyramidal neuronsBasal gangliaMotor hyperactivityReceptor antagonistInhibitory interneuronsTyrosine hydroxylaseCortical circuitsPsychiatric disordersLocomotor responseNeuronal subtypesReceptor 1Mutant miceDopamine transporterSpatial learningAstroglial Cells in Development, Regeneration, and Repair
Vaccarino FM, Fagel DM, Ganat Y, Maragnoli ME, Ment LR, Ohkubo Y, Schwartz ML, Silbereis J, Smith KM. Astroglial Cells in Development, Regeneration, and Repair. The Neuroscientist 2007, 13: 173-185. PMID: 17404377, DOI: 10.1177/1073858406298336.Peer-Reviewed Original Research In PressConceptsFibroblast growth factor receptorAstroglial cellsGenetic fate mappingCell divisionLineage studiesGrowth factor receptorPostnatal CNSEmbryonic CNSMain cellular componentsFate mappingNeuronal differentiationCellular componentsCell typesInjury-induced increaseFactor receptorNeurogenic nichePerinatal injuryCerebral cortexYoung miceCellsOligodendrocytesNeuronsDifferent rolesCNSNiche
2006
Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem Cells In Vivo
Ganat YM, Silbereis J, Cave C, Ngu H, Anderson GM, Ohkubo Y, Ment LR, Vaccarino FM. Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem Cells In Vivo. Journal Of Neuroscience 2006, 26: 8609-8621. PMID: 16914687, PMCID: PMC6674357, DOI: 10.1523/jneurosci.2532-06.2006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAstrocytesBrainCell DifferentiationCell LineageCerebral VentriclesDoublecortin ProteinFemaleGlial Fibrillary Acidic ProteinHumansIntegrasesMaleMiceMice, TransgenicNeuronsOlfactory BulbOligodendrogliaPromoter Regions, GeneticRecombination, GeneticStem CellsTransgenesConceptsDentate gyrusHuman GFAP promoterCerebral cortexAstroglial cellsSubventricular zoneOlfactory bulbPostnatal brainNeural progenitor/stem cellsPostnatal day 5First postnatal weekProgenitor/stem cellsStem cellsInducible Cre recombinaseNeural stem cellsGenetic fate mappingMature neuronsPostnatal weekCNS regionsWhite matterDay 5GFAP promoterNeural precursorsCortexNeuronsCre recombinaseMidline radial glia translocation and corpus callosum formation require FGF signaling
Smith KM, Ohkubo Y, Maragnoli ME, Rašin M, Schwartz ML, Šestan N, Vaccarino FM. Midline radial glia translocation and corpus callosum formation require FGF signaling. Nature Neuroscience 2006, 9: 787-797. PMID: 16715082, DOI: 10.1038/nn1705.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAstrocytesCell MovementCell ShapeCerebral CortexCorpus CallosumDown-RegulationFemaleFibroblast Growth Factor 8Fibroblast Growth FactorsGrowth ConesMaleMiceMice, KnockoutMice, TransgenicNeurogliaReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2RNA InterferenceSignal TransductionConceptsRadial glial cellsGlial cellsSomal translocationRadial gliaCorpus callosum formationReceptor 1 geneCallosal dysgenesisCerebral cortexFibroblast growth factor receptor 1 (FGFR1) geneIndusium griseumDorsomedial cortexDorsolateral cortexKnockout miceCortexAstrogliaApical endfeetFGFR1 geneAstrocytesGliaAxon guidanceDorsal midlinePrecise targetingCellsUnexpected roleFGFCortical neurogenesis enhanced by chronic perinatal hypoxia
Fagel DM, Ganat Y, Silbereis J, Ebbitt T, Stewart W, Zhang H, Ment LR, Vaccarino FM. Cortical neurogenesis enhanced by chronic perinatal hypoxia. Experimental Neurology 2006, 199: 77-91. PMID: 15916762, DOI: 10.1016/j.expneurol.2005.04.006.Peer-Reviewed Original ResearchConceptsChronic perinatal hypoxiaCerebral cortexPerinatal hypoxiaCortical neurogenesisCessation of hypoxiaInfant mouse brainSubcortical white matterLower cortical layersMature mammalian brainPostnatal day 3Forebrain subventricular zoneBrdU-positive cellsCortical neuron numberAstroglial cell proliferationNormoxic miceNeonatal injuryNeuronal lossBrain weightCortical neuronsNew neuronsCortical volumeNeuronal markersSubventricular zoneJuvenile micePutative neuroblasts
2004
Chronic neonatal hypoxia leads to long term decreases in the volume and cell number of the rat cerebral cortex
Schwartz ML, Vaccarino F, Chacon M, Yan WL, Ment LR, Stewart WB. Chronic neonatal hypoxia leads to long term decreases in the volume and cell number of the rat cerebral cortex. Seminars In Perinatology 2004, 28: 379-388. PMID: 15693394, DOI: 10.1053/j.semperi.2004.10.009.Peer-Reviewed Original ResearchConceptsDays of hypoxiaPreterm birth resultsNeuronal sizeBirth resultsHypoxic exposureCell numberChronic neonatal hypoxiaChronic sublethal hypoxiaNeonatal rodent modelPerinatal period altersRat cerebral cortexNeuronal cell numberBcl-2Glial cell numbersNormoxic environmentPostnatal day 3Cortical cell numberSignificant neurodevelopmental disabilitiesWestern blot analysisPreterm birthNeonatal hypoxiaNormoxic exposureCerebral cortexChronic hypoxiaControl pupsLoss of Glutamatergic Pyramidal Neurons in Frontal and Temporal Cortex Resulting from Attenuation of FGFR1 Signaling Is Associated with Spontaneous Hyperactivity in Mice
Shin DM, Korada S, Raballo R, Shashikant CS, Simeone A, Taylor JR, Vaccarino F. Loss of Glutamatergic Pyramidal Neurons in Frontal and Temporal Cortex Resulting from Attenuation of FGFR1 Signaling Is Associated with Spontaneous Hyperactivity in Mice. Journal Of Neuroscience 2004, 24: 2247-2258. PMID: 14999075, PMCID: PMC6730438, DOI: 10.1523/jneurosci.5285-03.2004.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-AgonistsAmphetamineAnimalsCell DifferentiationCell DivisionFrontal LobeGlutamic AcidGuanfacineHumansHyperkinesisMiceMice, TransgenicNervous System MalformationsNeural InhibitionPyramidal CellsReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptors, Adrenergic, alpha-2Receptors, Fibroblast Growth FactorSignal TransductionStereotypic Movement DisorderTemporal LobeConceptsPyramidal neuronsCortical developmentTemporal areaSubcortical monoaminergic systemsGlutamatergic pyramidal neuronsCajal-Retzius cellsCortical GABAergic interneuronsCerebral cortical developmentAdrenergic receptor agonistEmbryonic neural progenitor cellsTemporal cortical areasReceptor gene productsNeural progenitor cellsEmbryonic brain developmentLocomotor hyperactivityRadial glia fibersCerebral cortexGlutamatergic neuronsBasal gangliaGABAergic interneuronsMonoaminergic systemsCortical plateReceptor agonistSpontaneous hyperactivityCortical areas
2002
Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone
Ganat Y, Soni S, Chacon M, Schwartz ML, Vaccarino FM. Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone. Neuroscience 2002, 112: 977-991. PMID: 12088755, DOI: 10.1016/s0306-4522(02)00060-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCerebral CortexCerebral VentriclesEnzyme-Linked Immunosorbent AssayEpendymaFibroblast Growth Factor 1Fibroblast Growth Factor 2HypoxiaImmunohistochemistryNeurogliaRatsReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Receptors, Fibroblast Growth FactorRegenerationUp-RegulationConceptsRadial glial cellsRadial gliaChronic hypoxiaGlial cellsFibroblast growth factor 1Periventricular regionBrain lipid binding proteinMajor receptorChronic hypoxic damageGlial fibrillary acidic proteinHypoxia/ischemiaSub-ventricular zoneImmature glial cellsFibrillary acidic proteinGrowth factor-1Ependymal zoneChronic hypoxemiaCerebral cortexHypoxic damageNeurotrophin familyPerinatal brainFGF receptor 1Rat pupsPostnatal weekGlial phenotypeFibroblast Growth Factor 2 Is Necessary for the Growth of Glutamate Projection Neurons in the Anterior Neocortex
Korada S, Zheng W, Basilico C, Schwartz ML, Vaccarino FM. Fibroblast Growth Factor 2 Is Necessary for the Growth of Glutamate Projection Neurons in the Anterior Neocortex. Journal Of Neuroscience 2002, 22: 863-875. PMID: 11826116, PMCID: PMC6758485, DOI: 10.1523/jneurosci.22-03-00863.2002.Peer-Reviewed Original ResearchConceptsCerebral cortexParietal cortexAnterior cerebral cortexGlutamatergic pyramidal neuronsGABA receptor agonistsGlutamatergic neuronal populationsDuration of sleepAnterior cortical regionsBasic fibroblast growth factorCell numberNull mutant miceGranule cell numberFibroblast growth factor-2Fibroblast growth factorGABA interneuronsGrowth factor 2Fgf2-/- micePyramidal neuronsInhibitory neurotransmissionProjection neuronsAnterior neocortexReceptor agonistPyramidal cellsOccipital cortexNeuronal populations
2000
Basic Fibroblast Growth Factor (Fgf2) Is Necessary for Cell Proliferation and Neurogenesis in the Developing Cerebral Cortex
Raballo R, Rhee J, Lyn-Cook R, Leckman J, Schwartz M, Vaccarino F. Basic Fibroblast Growth Factor (Fgf2) Is Necessary for Cell Proliferation and Neurogenesis in the Developing Cerebral Cortex. Journal Of Neuroscience 2000, 20: 5012-5023. PMID: 10864959, PMCID: PMC6772267, DOI: 10.1523/jneurosci.20-13-05012.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell DivisionCerebral CortexChoroid PlexusEmbryonic and Fetal DevelopmentFibroblast Growth Factor 2Gene Expression Regulation, DevelopmentalGerm-Line MutationGestational AgeMiceMice, KnockoutProsencephalonReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptors, Fibroblast Growth FactorTelencephalonConceptsFgf2 knockout micePseudostratified ventricular epitheliumKnockout miceCerebral cortexCortical neuronsFrontal cerebral cortexDeep cortical layersBasic fibroblast growth factorEnd of neurogenesisCortical neuron numberNeuronal progenitor cellsNull mutant miceBasic fibroblast growth factor (bFGF) geneFibroblast growth factorDegree of apoptosisLarge neuronsBasal gangliaCortical layersFgf2 knockoutGrowth factor geneMutant miceVentricular epitheliumGermline mutationsNeuron numberNeurogenesis
1999
Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis
Vaccarino F, Schwartz M, Raballo R, Nilsen J, Rhee J, Zhou M, Doetschman T, Coffin J, Wyland J, Hung Y. Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nature Neuroscience 1999, 2: 246-253. PMID: 10195217, DOI: 10.1038/6350.Peer-Reviewed Original ResearchConceptsPseudostratified ventricular epitheliumFibroblast growth factor-2Number of gliaAdult cerebral cortexEnd of neurogenesisCerebral cortex sizeFibroblast growth factorGrowth factor 2Cerebral cortexCerebral ventricleSingle microinjectionCortical neuronsBrdU studiesCortical progenitorsVentricular epitheliumCortex sizeGrowth factorRat embryosFGF2 geneEarly neurogenesisFGF receptorsFactor 2GliaNeurogenesisCell cycle length6 Fibroblast Growth Factor Signaling Regulates Growth and Morphogenesis at Multiple Steps during Brain Development11This work represents a collaboration between the laboratories of the first two authors.
Vaccarino F, Schwartz M, Raballo R, Rhee J, Lyn-Cook R. 6 Fibroblast Growth Factor Signaling Regulates Growth and Morphogenesis at Multiple Steps during Brain Development11This work represents a collaboration between the laboratories of the first two authors. Current Topics In Developmental Biology 1999, 46: 179-200. PMID: 10417880, DOI: 10.1016/s0070-2153(08)60329-4.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsCentral nervous system regionsNervous system regionsCentral nervous systemRole of FGF2Growth factor familyCerebral cortexFibroblast growth factor (FGF) familyCortical developmentNervous systemFibroblast growth factor (FGF) signalingGrowth factor signalingSystem regionsFactor signalingMolecular mechanismsCoordinated activationDistinct patternsTarget genesFGF2FGFFactor familyCortex
1995
Basic Fibroblast Growth Factor Increases the Number of Excitatory Neurons Containing Glutamate in the Cerebral Cortex
Vaccarino F, Schwartz M, Hartigan D, Leckman J. Basic Fibroblast Growth Factor Increases the Number of Excitatory Neurons Containing Glutamate in the Cerebral Cortex. Cerebral Cortex 1995, 5: 64-78. PMID: 7719131, DOI: 10.1093/cercor/5.1.64.Peer-Reviewed Original ResearchConceptsBasic fibroblast growth factorNerve growth factorGlutamate-containing neuronsCerebral cortexFibroblast growth factorGrowth factorAspartate-containing neuronsDifferent neurotransmitter phenotypesNumber of GABARatio of glutamateStem cellsNeurotransmitter phenotypeExcitatory neuronsInhibitory neuronsRat telencephalonVentricular zoneBFGF mRNAGABANeuronsCortexGlutamateDiffusible factorsThreefold increaseCellsFactors
1994
Excitatory amino acid receptors in glial progenitor cells: Molecular and functional properties
Gallo V, Patneau D, Mayer M, Vaccarino F. Excitatory amino acid receptors in glial progenitor cells: Molecular and functional properties. Glia 1994, 11: 94-101. PMID: 7927651, DOI: 10.1002/glia.440110204.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH Keywords6-Cyano-7-nitroquinoxaline-2,3-dioneAnimalsCells, CulturedCerebral CortexDNA-Binding ProteinsEarly Growth Response Protein 1Gene Expression RegulationGenes, Immediate-EarlyGlutamic AcidImmediate-Early ProteinsKainic AcidMembrane PotentialsNerve Tissue ProteinsNeurotoxinsN-MethylaspartateOligodendrogliaRatsReceptors, GlutamateStem CellsTranscription FactorsConceptsCG-4 cellsAMPA receptor antagonist CNQXWhole-cell patch-clamp recordingsExcitatory amino acid receptorsProgenitor cellsAmino acid receptorsRat cerebral cortexPatch-clamp recordingsGlial progenitor cellsGlutamate receptor subunitsAgonists L-glutamateGlutamate-gated channelsImmediate early gene NGFIAntagonist CNQXCerebral cortexGABA antibodyPrimary cell linesGlutamate receptorsTransient elevationAcid receptorsReceptor subunitsOligodendrocyte lineageOligodendrocyte progenitorsL-glutamateKainate
1993
Induction of immediate early genes by cyclic AMP in primary cultures of neurons from rat cerebral cortex
Vaccarino FM, Hayward MD, Le HN, Hartigan DJ, Duman RS, Nestler EJ. Induction of immediate early genes by cyclic AMP in primary cultures of neurons from rat cerebral cortex. Brain Research 1993, 19: 76-82. PMID: 8103187, DOI: 10.1016/0169-328x(93)90151-e.Peer-Reviewed Original ResearchMeSH Keywords2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepineAnimalsAnimals, NewbornBucladesineCells, CulturedCerebral CortexColforsinCyclic AMPDNA-Binding ProteinsDopamine AgentsEarly Growth Response Protein 1ErgolinesGene Expression RegulationGenes, fosGenes, junGlutamatesGlutamic AcidImmediate-Early ProteinsImmunohistochemistryKineticsNeurogliaNeuronsQuinpiroleRatsRNA, MessengerSecond Messenger SystemsTranscription FactorsVasoactive Intestinal PeptideConceptsVasoactive intestinal peptideRat cerebral cortexCerebral cortexExcitatory amino acid receptor antagonistsDibutyryl cAMPAmino acid receptor antagonistsPrimary culturesC-fosDihydropyridine-sensitive calcium channelsAcid receptor antagonistsIEG inductionCalcium-free mediumCAMP second messenger pathwayIEGs c-fosSKF 38393Immediate-early gene transcription factorsIntestinal peptideReceptor antagonistReceptor agonistSecond messenger pathwaysCalcium channelsDifferentiated neuronsBrief stimulationImmediate early genesIEG expression