Featured Publications
Enhanced FIB-SEM systems for large-volume 3D imaging
Xu CS, Hayworth KJ, Lu Z, Grob P, Hassan AM, García-Cerdán JG, Niyogi KK, Nogales E, Weinberg RJ, Hess HF. Enhanced FIB-SEM systems for large-volume 3D imaging. ELife 2017, 6: e25916. PMID: 28500755, PMCID: PMC5476429, DOI: 10.7554/elife.25916.Peer-Reviewed Original ResearchConceptsFIB-SEM systemFocused Ion Beam Scanning Electron MicroscopyIon beam scanning electron microscopyBeam scanning electron microscopyLong-term system stabilityScanning electron microscopyNovel high-resolution techniqueSystem stabilityFIB-SEMElectron microscopyHigh resolutionHigh-resolution techniquesSmall volumeA connectome and analysis of the adult Drosophila central brain
Scheffer LK, Xu CS, Januszewski M, Lu Z, Takemura SY, Hayworth KJ, Huang GB, Shinomiya K, Maitlin-Shepard J, Berg S, Clements J, Hubbard PM, Katz WT, Umayam L, Zhao T, Ackerman D, Blakely T, Bogovic J, Dolafi T, Kainmueller D, Kawase T, Khairy KA, Leavitt L, Li PH, Lindsey L, Neubarth N, Olbris DJ, Otsuna H, Trautman ET, Ito M, Bates AS, Goldammer J, Wolff T, Svirskas R, Schlegel P, Neace E, Knecht CJ, Alvarado CX, Bailey DA, Ballinger S, Borycz JA, Canino BS, Cheatham N, Cook M, Dreher M, Duclos O, Eubanks B, Fairbanks K, Finley S, Forknall N, Francis A, Hopkins GP, Joyce EM, Kim S, Kirk NA, Kovalyak J, Lauchie S, Lohff A, Maldonado C, Manley EA, McLin S, Mooney C, Ndama M, Ogundeyi O, Okeoma N, Ordish C, Padilla N, Patrick CM, Paterson T, Phillips EE, Phillips EM, Rampally N, Ribeiro C, Robertson MK, Rymer JT, Ryan SM, Sammons M, Scott AK, Scott AL, Shinomiya A, Smith C, Smith K, Smith NL, Sobeski MA, Suleiman A, Swift J, Takemura S, Talebi I, Tarnogorska D, Tenshaw E, Tokhi T, Walsh JJ, Yang T, Horne JA, Li F, Parekh R, Rivlin PK, Jayaraman V, Costa M, Jefferis GS, Ito K, Saalfeld S, George R, Meinertzhagen I, Rubin GM, Hess HF, Jain V, Plaza SM. A connectome and analysis of the adult Drosophila central brain. ELife 2020, 9: e57443. PMID: 32880371, PMCID: PMC7546738, DOI: 10.7554/elife.57443.Peer-Reviewed Original ResearchConceptsCentral brainDrosophila central brainAdult Drosophila Central BrainGenetic reagentsFruit flyComputational compartmentsFly brainExhaustive atlasCell typesAnimal behaviorNeural motifsChemical synapsesDrosophilaSuch large data setsNeural circuitsFliesCompartmentalizationLarge fractionMotifSynapsesCell exampleCompartmentsNeuronsElectrical consequencesContacts between the endoplasmic reticulum and other membranes in neurons
Wu Y, Whiteus C, Xu CS, Hayworth KJ, Weinberg RJ, Hess HF, De Camilli P. Contacts between the endoplasmic reticulum and other membranes in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e4859-e4867. PMID: 28559323, PMCID: PMC5474793, DOI: 10.1073/pnas.1701078114.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulumER–plasma membrane contactsER-PM contactsMembrane contactSmaller focal contactsRegulation of CaInterorganelle communicationOrganelle biogenesisDifferent neuronal compartmentsCell physiologyIntracellular membranesFocal contactsMultivesicular bodiesER contactsIntracellular organellesER cisternaeLipid homeostasisBiochemical studiesTubulovesicular structuresMembrane appositionNeuronal compartmentsImportant functionsMitochondriaReticulumMembrane
2022
En bloc preparation of Drosophila brains enables high-throughput FIB-SEM connectomics
Lu Z, Xu C, Hayworth K, Pang S, Shinomiya K, Plaza S, Scheffer L, Rubin G, Hess H, Rivlin P, Meinertzhagen I. En bloc preparation of Drosophila brains enables high-throughput FIB-SEM connectomics. Frontiers In Neural Circuits 2022, 16: 917251. PMID: 36589862, PMCID: PMC9801301, DOI: 10.3389/fncir.2022.917251.Peer-Reviewed Original Research
2019
Gas cluster ion beam SEM for imaging of large tissue samples with 10 nm isotropic resolution
Hayworth K, Peale D, Januszewski M, Knott G, Lu Z, Xu C, Hess H. Gas cluster ion beam SEM for imaging of large tissue samples with 10 nm isotropic resolution. Nature Methods 2019, 17: 68-71. PMID: 31740820, DOI: 10.1038/s41592-019-0641-2.Peer-Reviewed Original ResearchConceptsIon beam scanning electron microscopyBeam scanning electron microscopyScanning electron microscopyThree-dimensional electron microscopy techniquesElectron microscopy techniquesIon millingIsotropic resolutionMicroscopy techniquesElectron microscopyThick tissue sectionsResolutionLarge tissue samplesMicroscopyMillingSectionsNeuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity
Ioannou MS, Jackson J, Sheu SH, Chang CL, Weigel AV, Liu H, Pasolli HA, Xu CS, Pang S, Matthies D, Hess HF, Lippincott-Schwartz J, Liu Z. Neuron-Astrocyte Metabolic Coupling Protects against Activity-Induced Fatty Acid Toxicity. Cell 2019, 177: 1522-1535.e14. PMID: 31130380, DOI: 10.1016/j.cell.2019.04.001.Peer-Reviewed Original ResearchConceptsGene expression programsLipid dropletsFatty acidsToxic fatty acidsMitochondrial β-oxidationNeuron-astrocyte couplingExpression programsMetabolic coordinationFatty acid toxicityFA toxicityCoordinated mechanismFA metabolismΒ-oxidationLipid metabolismHyperactive neuronsAcid toxicityNeuronal activityDisease statesNeuronsMetabolismNeural activityLipid particlesAstrocytesBrainHomeostasisCortical column and whole-brain imaging with molecular contrast and nanoscale resolution
Gao R, Asano SM, Upadhyayula S, Pisarev I, Milkie DE, Liu TL, Singh V, Graves A, Huynh GH, Zhao Y, Bogovic J, Colonell J, Ott CM, Zugates C, Tappan S, Rodriguez A, Mosaliganti KR, Sheu SH, Pasolli HA, Pang S, Xu CS, Megason SG, Hess H, Lippincott-Schwartz J, Hantman A, Rubin GM, Kirchhausen T, Saalfeld S, Aso Y, Boyden ES, Betzig E. Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution. Science 2019, 363 PMID: 30655415, PMCID: PMC6481610, DOI: 10.1126/science.aau8302.Peer-Reviewed Original ResearchConceptsDopaminergic neuronsDendritic spinesMouse cortexPresynaptic densitySynaptic proteinsBrain regionsLarge-scale studiesCortical columnsLattice light-sheet microscopyNeural activityNeural developmentSpecific molecular constituentsBrainLight-sheet microscopyDegree of stereotypyNanoscale spatial relationshipExpansion microscopyComparisons between the ON- and OFF-edge motion pathways in the Drosophila brain
Shinomiya K, Huang G, Lu Z, Parag T, Xu CS, Aniceto R, Ansari N, Cheatham N, Lauchie S, Neace E, Ogundeyi O, Ordish C, Peel D, Shinomiya A, Smith C, Takemura S, Talebi I, Rivlin PK, Nern A, Scheffer LK, Plaza SM, Meinertzhagen IA. Comparisons between the ON- and OFF-edge motion pathways in the Drosophila brain. ELife 2019, 8: e40025. PMID: 30624205, PMCID: PMC6338461, DOI: 10.7554/elife.40025.Peer-Reviewed Original Research
2018
The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles
Coulter ME, Dorobantu CM, Lodewijk GA, Delalande F, Cianferani S, Ganesh VS, Smith RS, Lim ET, Xu CS, Pang S, Wong ET, Lidov HGW, Calicchio ML, Yang E, Gonzalez DM, Schlaeger TM, Mochida GH, Hess H, Lee WA, Lehtinen MK, Kirchhausen T, Haussler D, Jacobs FMJ, Gaudin R, Walsh CA. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles. Cell Reports 2018, 24: 973-986.e8. PMID: 30044992, PMCID: PMC6178983, DOI: 10.1016/j.celrep.2018.06.100.Peer-Reviewed Original ResearchConceptsExtracellular vesiclesMultivesicular bodiesIntraluminal vesicle formationESCRT proteinsHedgehog secretionProgenitor maintenanceMolecular mechanistic insightsComplex proteinsCell communicationEV subtypesVesicle formationChmp1AAutosomal recessive microcephalyHuman cerebral organoidsSonic hedgehogProgenitor proliferationFunction mutationsImpairs secretionAdult functionMechanistic insightsCerebral organoidsNull micePontocerebellar hypoplasiaShhProtein
2015
Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics
Hayworth K, Xu C, Lu Z, Knott G, Fetter R, Tapia J, Lichtman J, Hess H. Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics. Nature Methods 2015, 12: 319-322. PMID: 25686390, PMCID: PMC4382383, DOI: 10.1038/nmeth.3292.Peer-Reviewed Original Research