Featured Publications
Automated time-lapse data segmentation reveals in vivo cell state dynamics
Genuth M, Kojima Y, Jülich D, Kiryu H, Holley S. Automated time-lapse data segmentation reveals in vivo cell state dynamics. Science Advances 2023, 9: eadf1814. PMID: 37267354, PMCID: PMC10413672, DOI: 10.1126/sciadv.adf1814.Peer-Reviewed Original ResearchConceptsCell statesSingle-cell RNA sequencing dataCell state dynamicsCell behaviorEmbryonic development proceedsCell state transitionsRNA sequencing dataCollective cell behaviorIndividual cell behaviorsZebrafish tailbudLeft-right asymmetryCell tracking dataCollective cell motionGene expressionSequencing dataMolecular processesIndividual embryosDevelopment proceedsEmbryosCell motionParallel identificationBilateral symmetryReproducible patternTailbudState transitionsIntegrin intra-heterodimer affinity inversely correlates with integrin activatability
Sun G, Guillon E, Holley SA. Integrin intra-heterodimer affinity inversely correlates with integrin activatability. Cell Reports 2021, 35: 109230. PMID: 34107244, PMCID: PMC8227800, DOI: 10.1016/j.celrep.2021.109230.Peer-Reviewed Original ResearchConceptsFluorescence cross-correlation spectroscopyCell surface expressionHeterodimeric cell surface receptorsPoor cell surface expressionCell surface stabilityRobust cell surface expressionExtracellular matrix proteinsCell surface receptorsZebrafish somitogenesisSurface expressionCross-correlation spectroscopyFluorescence resonance energy transferIntegrin activationΒ-subunitIntegrin heterodimersFibronectin matrixMatrix proteinsVivo contextConformational changesCell adhesionResonance energy transferSurface receptorsIntegrin αvβ1Biophysical measurementsIntegrinsFibronectin is a smart adhesive that both influences and responds to the mechanics of early spinal column development
Guillon E, Das D, Jülich D, Hassan AR, Geller H, Holley S. Fibronectin is a smart adhesive that both influences and responds to the mechanics of early spinal column development. ELife 2020, 9: e48964. PMID: 32228864, PMCID: PMC7108867, DOI: 10.7554/elife.48964.Peer-Reviewed Original ResearchConceptsNeural tubeParaxial mesodermZebrafish neural tubeNormal vertebrate developmentVertebrate trunkVertebrate developmentFibronectin remodelingFibronectin matrixConvergence defectsMorphogenesisExtracellular matrixMesodermFibronectinColumn developmentSmart adhesivesCadherinMutantsAdhesive lap jointsAdhesionLap jointsSymmetric interfacesRemodelingShear stressDefectsOrganization of Embryonic Morphogenesis via Mechanical Information
Das D, Jülich D, Schwendinger-Schreck J, Guillon E, Lawton AK, Dray N, Emonet T, O'Hern CS, Shattuck MD, Holley SA. Organization of Embryonic Morphogenesis via Mechanical Information. Developmental Cell 2019, 49: 829-839.e5. PMID: 31178400, PMCID: PMC6590525, DOI: 10.1016/j.devcel.2019.05.014.Peer-Reviewed Original ResearchConceptsEmbryonic organizerCell motionCell polarityTransgenic perturbationsEmbryonic morphogenesisMorphogen signalingTail organizerZebrafish embryosCell movementMechanical informationCell adhesionCell contractilityNeighboring cellsLocal biochemicalEmbryosMorphogenesisSecondary consequenceAdditional mechanismCellsMorphogensTranscriptionSignalingSystematic analysisOrganizersComputational modelingPatterned Disordered Cell Motion Ensures Vertebral Column Symmetry
Das D, Chatti V, Emonet T, Holley SA. Patterned Disordered Cell Motion Ensures Vertebral Column Symmetry. Developmental Cell 2017, 42: 170-180.e5. PMID: 28743003, PMCID: PMC5568629, DOI: 10.1016/j.devcel.2017.06.020.Peer-Reviewed Original ResearchCross-Scale Integrin Regulation Organizes ECM and Tissue Topology
Jülich D, Cobb G, Melo AM, McMillen P, Lawton AK, Mochrie SG, Rhoades E, Holley SA. Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology. Developmental Cell 2015, 34: 33-44. PMID: 26096733, PMCID: PMC4496283, DOI: 10.1016/j.devcel.2015.05.005.Peer-Reviewed Original ResearchConceptsExtracellular matrixCadherin-2Integrin α5Cell-cell adhesionFluorescence cross-correlation spectroscopyECM protein fibronectinSomite boundariesCross-correlation spectroscopyAdjacent cell membranesBody elongationECM assemblyIntegrin associationIntegrin activationPhysical associationActive conformationFibronectin fibrillogenesisProtein fibronectinTissue assemblyIntegrin conformationTissue topologyInactive integrinsCell membraneCross-scale mechanismsStereotypic patternAnimal tissues
2024
Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer’s disease
Bhattarai P, Gunasekaran T, Belloy M, Reyes-Dumeyer D, Jülich D, Tayran H, Yilmaz E, Flaherty D, Turgutalp B, Sukumar G, Alba C, McGrath E, Hupalo D, Bacikova D, Le Guen Y, Lantigua R, Medrano M, Rivera D, Recio P, Nuriel T, Ertekin-Taner N, Teich A, Dickson D, Holley S, Greicius M, Dalgard C, Zody M, Mayeux R, Kizil C, Vardarajan B. Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer’s disease. Acta Neuropathologica 2024, 147: 70. PMID: 38598053, PMCID: PMC11006751, DOI: 10.1007/s00401-024-02721-1.Peer-Reviewed Original ResearchConceptsLoss-of-functionWhole-genome sequencingFibronectin 1Genetic variationAlzheimer's diseaseAD riskRare coding variantsLoss-of-function variantsRare genetic variationGene Ontology termsFamily based studyIn vivo functional studiesAD-related pathologyAlpha 2 chainOntology termsPresence of cellular mechanismsProtective variantsECM proteinsAD pathologyPathway analysisFunctional studiesUnaffected carriersZebrafish modelAPOEe4 alleleProtein levels
2016
A Sawtooth Pattern of Cadherin 2 Stability Mechanically Regulates Somite Morphogenesis
McMillen P, Chatti V, Jülich D, Holley SA. A Sawtooth Pattern of Cadherin 2 Stability Mechanically Regulates Somite Morphogenesis. Current Biology 2016, 26: 542-549. PMID: 26853361, PMCID: PMC4822709, DOI: 10.1016/j.cub.2015.12.055.Peer-Reviewed Original ResearchConceptsECM assemblyGenetic mosaicsPosterior somitesDifferential cadherin expressionExtracellular matrixCell-ECM adhesionFN matrix assemblyBoundary formationVertebrate gastrulationSomite boundariesSomite morphogenesisCytoskeletal contractilityParaxial mesodermEmbryonic precursorsCDH activityMatrix assemblyCadherin expressionCDH2SomitesTissue boundariesIntegrin α5SomitogenesisCell sortingCell aggregatesAssembly
2013
Cell-Fibronectin Interactions Propel Vertebrate Trunk Elongation via Tissue Mechanics
Dray N, Lawton A, Nandi A, Jülich D, Emonet T, Holley SA. Cell-Fibronectin Interactions Propel Vertebrate Trunk Elongation via Tissue Mechanics. Current Biology 2013, 23: 1335-1341. PMID: 23810535, PMCID: PMC3725194, DOI: 10.1016/j.cub.2013.05.052.Peer-Reviewed Original ResearchConceptsCell migrationTrunk elongationExtracellular matrixCell-FN interactionsTransgenic rescue experimentsECM protein fibronectinElongation defectsParaxial mesodermBody elongationEmbryonic developmentTissue homeostasisTail budTissue mechanicsΑ-subunitRescue experimentsProtein fibronectinSystem-level analysisCell adhesionFN matrixIntegrin α5Concomitant lossTissue integrityCell motionITGαvFibronectinRegulated tissue fluidity steers zebrafish body elongation
Lawton AK, Nandi A, Stulberg MJ, Dray N, Sneddon MW, Pontius W, Emonet T, Holley SA. Regulated tissue fluidity steers zebrafish body elongation. Development 2013, 140: 573-582. PMID: 23293289, PMCID: PMC3561786, DOI: 10.1242/dev.090381.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedBiomechanical PhenomenaBody PatterningCadherinsCell AdhesionCell CountCell MovementCell PolarityComputer SimulationEmbryo, NonmammalianEmbryonic DevelopmentFibroblast Growth FactorsGene Expression Regulation, DevelopmentalModels, BiologicalTailTime FactorsWnt Signaling PathwayZebrafishZebrafish Proteins
2012
Crosstalk between Fgf and Wnt signaling in the zebrafish tailbud
Stulberg MJ, Lin A, Zhao H, Holley SA. Crosstalk between Fgf and Wnt signaling in the zebrafish tailbud. Developmental Biology 2012, 369: 298-307. PMID: 22796649, PMCID: PMC3423502, DOI: 10.1016/j.ydbio.2012.07.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceDNA PrimersFibroblast Growth FactorsGene Expression Regulation, DevelopmentalGene Regulatory NetworksGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMAP Kinase Signaling SystemModels, BiologicalPhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktSignal TransductionTailWnt Signaling PathwayZebrafishZebrafish ProteinsConceptsZebrafish tailbudCell fate specificationCell fate changesCo-regulated genesWnt antagonist Dkk1Reciprocal positive regulationFate specificationFate changesNascent transcriptionAxis elongationProtein phosphorylationPhosphorylation of GSK3βPI3-kinaseFGF pathwayMesodermal developmentTail elongationPositive regulationTarget genesAntagonist DKK1TailbudFibroblast growth factorWntPhosphorylation levelsTranscriptionGSK3β phosphorylationThe Her7 node modulates the network topology of the zebrafish segmentation clock via sequestration of the Hes6 hub
Trofka A, Schwendinger-Schreck J, Brend T, Pontius W, Emonet T, Holley SA. The Her7 node modulates the network topology of the zebrafish segmentation clock via sequestration of the Hes6 hub. Development 2012, 139: 940-947. PMID: 22278920, PMCID: PMC3274355, DOI: 10.1242/dev.073544.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsBiological ClocksBody PatterningComputer SimulationDimerizationDNAGene Expression Regulation, DevelopmentalGene Knockdown TechniquesGene Regulatory NetworksRecombinant Fusion ProteinsRepressor ProteinsTranscription FactorsZebrafishZebrafish ProteinsConceptsZebrafish segmentation clockSegmentation clockBinds DNACis-regulatory sequencesDNA-binding heterodimersTranscriptional negative feedbackGenetic experimentsHer7Regulatory sequencesDNA bindingHes6Vivo assaysDNAHomodimerHeterodimersDistinct preferenceEmergent functionsNetwork hubsNegative feedbackComputational analysisClockDimersSequestrationProteinRegulation
2009
Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling
Jülich D, Mould AP, Koper E, Holley SA. Control of extracellular matrix assembly along tissue boundaries via Integrin and Eph/Ephrin signaling. Development 2009, 136: 2913-2921. PMID: 19641014, DOI: 10.1242/dev.038935.Peer-Reviewed Original Research
2008
Segmentation of touching cell nuclei using gradient flow tracking
LI G, LIU T, NIE J, GUO L, CHEN J, ZHU J, XIA W, MARA A, HOLLEY S, WONG S. Segmentation of touching cell nuclei using gradient flow tracking. Journal Of Microscopy 2008, 231: 47-58. PMID: 18638189, DOI: 10.1111/j.1365-2818.2008.02016.x.Peer-Reviewed Original Research
2005
beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation
Jülich D, Lim C, Round J, Nicolaije C, Schroeder J, Davies A, Geisler R, Lewis J, Jiang Y, Holley S, Consortium T. beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation. Developmental Biology 2005, 286: 391-404. PMID: 16125692, DOI: 10.1016/j.ydbio.2005.06.040.Peer-Reviewed Original ResearchConceptsPresomitic mesodermSomite segmentationZebrafish genetic screenEGF repeatsGenetic screenOscillating expressionOscillating genesSegmentation clockDouble mutantDSL domainSubcellular localizationAntimorphic effectsStrong defectsGene expressionNotch pathwayNotch ligandsNew allelesIndividual cellsDeltaCTriple fluorescentCoordinated oscillationsGenesAllelesExpressionLigand functionsIntegrinα5 and Delta/Notch Signaling Have Complementary Spatiotemporal Requirements during Zebrafish Somitogenesis
Ju¨lich D, Geisler R, Consortium T, Holley S. Integrinα5 and Delta/Notch Signaling Have Complementary Spatiotemporal Requirements during Zebrafish Somitogenesis. Developmental Cell 2005, 8: 575-586. PMID: 15809039, DOI: 10.1016/j.devcel.2005.01.016.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnimals, Genetically ModifiedBody PatterningCell PolarityExtracellular MatrixFibronectinsGene Expression Regulation, DevelopmentalIn Situ HybridizationIntegrin alpha5Intracellular Signaling Peptides and ProteinsMembrane ProteinsMolecular Sequence DataMorphogenesisPhenotypePoint MutationReceptors, NotchRecombinant Fusion ProteinsSignal TransductionSomitesZebrafishZebrafish ProteinsConceptsFibronectin matrix assemblyDelta/Notch signalingMatrix assemblyNotch pathway mutantsEntire body axisZebrafish somitogenesisVertebrate embryogenesisPathway mutantsDouble mutantSomite defectsSomite formationPosterior somitesGenetic controlSomitogenesisNotch signalingNotch pathwayEpithelial transitionSpatiotemporal requirementsBody axisCell polarizationSegmentation defectsPoint mutationsMutantsComplete lossSkeletal muscle
2000
Control of her1 expression during zebrafish somitogenesis by a Delta-dependent oscillator and an independent wave-front activity
Holley S, Geisler R, Nüsslein-Volhard C. Control of her1 expression during zebrafish somitogenesis by a Delta-dependent oscillator and an independent wave-front activity. Genes & Development 2000, 14: 1678-1690. PMID: 10887161, PMCID: PMC316735, DOI: 10.1101/gad.14.13.1678.Peer-Reviewed Original ResearchConceptsAnterior presomitic mesodermPresomitic mesodermGene expressionNotch pathwayHER1 expressionZebrafish genesZebrafish somitogenesisEmbryos mutantSomite morphogenesisMolecular clockExpression patternsExpression de novoExpression oscillatesNotch ligandsPathway upstreamSomitogenesisBorder formationConsecutive somitesDe novoSomitesExpressionWave-front modelPathwayClockHER1
1999
A radiation hybrid map of the zebrafish genome
Geisler R, Rauch G, Baier H, van Bebber F, Broβ L, Dekens M, Finger K, Fricke C, Gates M, Geiger H, Geiger-Rudolph S, Gilmour D, Glaser S, Gnügge L, Habeck H, Hingst K, Holley S, Keenan J, Kirn A, Knaut H, Lashkari D, Maderspacher F, Martyn U, Neuhauss S, Neumann C, Nicolson T, Pelegri F, Ray R, Rick J, Roehl H, Roeser T, Schauerte H, Schier A, Schönberger U, Schönthaler H, Schulte-Merker S, Seydler C, Talbot W, Weiler C, Nüsslein-Volhard C, Haffter P. A radiation hybrid map of the zebrafish genome. Nature Genetics 1999, 23: 86-89. PMID: 10471505, DOI: 10.1038/12692.Peer-Reviewed Original ResearchConceptsSimple sequence length polymorphismsZebrafish genomeRadiation hybrid mapCandidate genesLarge-scale mutagenesis screensSomatic cell hybrid linesSequence tagged site (STS) markersHybrid mapForward genetic approachGenome-wide mapsTagged site (STS) markersSequence length polymorphismsDensity of markersSignificant linkageRodent cell linesVertebrate organismsGenetic mappingDevelopmental controlMutagenesis screenRadiation-induced breakpointsSpecies of interestPositional cloningRH panelGenetic approachesRetention frequency8 Somitogenesis in Zebrafish
Holley S, Nüsslein-Volhard C. 8 Somitogenesis in Zebrafish. Current Topics In Developmental Biology 1999, 47: 247-277. PMID: 10595307, DOI: 10.1016/s0070-2153(08)60727-9.Peer-Reviewed Original ResearchConceptsSomite segmentationSegment polarity genesSpecific muscle typesExtension of axonsPolarity genesNotochord formationDanio rerioSomite developmentGenetic analysisMedial somiteMutantsSomitesGenesEmbryological studiesPrimary motoneuronsSomitogenesisSlow muscle fibersZebrafishNotochordMuscle typesDevelopment of motoneuronsDifferentiationMorphological transitionDrosophilaRerio
1998
Zebrafish segmentation and pair‐rule patterning
van Eeden F, Holley S, Haffter P, Nüsslein‐Volhard C. Zebrafish segmentation and pair‐rule patterning. Genesis 1998, 23: 65-76. PMID: 9706695, DOI: 10.1002/(sici)1520-6408(1998)23:1<65::aid-dvg7>3.0.co;2-4.Peer-Reviewed Original ResearchConceptsDrosophila segment polarity geneSegment polarity genesPair-rule patterningParaxial mesodermZebrafish homologueSomite boundariesPolarity genesPair-rule gene hairyPair-rule genesPair-rule phenotypeWild-type embryosGroup of genesGroup of mutantsGenetic screenVertebrate embryosDouble mutantSomite formationZebrafish segmentationHairy phenotypeMutantsMesodermSonic hedgehogGenesHomologuesHER1 expression