2025
Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines
Scuderi S, Kang T, Jourdon A, Nelson A, Yang L, Wu F, Anderson G, Mariani J, Tomasini L, Sarangi V, Abyzov A, Levchenko A, Vaccarino F. Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines. Cell Stem Cell 2025, 32: 970-989.e11. PMID: 40315847, PMCID: PMC12145255, DOI: 10.1016/j.stem.2025.04.006.Peer-Reviewed Original ResearchConceptsGradient of WntGene expression programsSingle-cell transcriptomicsBrain lineagesMorphogen gradientsEpigenetic variationDorso-ventral axisShh signalingExpression programsMorphogenFetal human brainHuman iPSC linesPluripotent stem cellsCell linesNeuronal lineageNeural tubeShhWntLineagesLine-to-line variationEarly patterningPattern systemPattern variationHuman brain regionsIPSC linesCACNA1G, A Heterotaxy Candidate Gene, Plays a Role in Ciliogenesis and Left‐Right Patterning in Xenopus tropicalis
Kostiuk V, Kabir R, Akbari R, Rushing A, González D, Kim A, Kim A, Zenisek D, Khokha M. CACNA1G, A Heterotaxy Candidate Gene, Plays a Role in Ciliogenesis and Left‐Right Patterning in Xenopus tropicalis. Genesis 2025, 63: e70009. PMID: 40008628, PMCID: PMC11867209, DOI: 10.1002/dvg.70009.Peer-Reviewed Original ResearchConceptsCongenital heart diseaseCACNA1GLow-voltage-activated calcium channelsExpression of Cacna1gCalcium channelsPatient cohortCardiac functionLR patterningHeterotaxyLR organizerChannel familyCACNA1SHeart diseaseLeft-rightG expressionXenopus tropicalisAbnormal expressionProcess of cilia formationCardiac loopingMultiple organsSignaling cascadesLR asymmetryPatientsT-typeEmbryonic developmentBiology of Hox Genes: Questions and Technological Challenges
Parambil S, De Kumar B. Biology of Hox Genes: Questions and Technological Challenges. Methods In Molecular Biology 2025, 2889: 1-10. PMID: 39745601, DOI: 10.1007/978-1-0716-4322-8_1.Peer-Reviewed Original Research
2024
Mannose controls mesoderm specification and symmetry breaking in mouse gastruloids
Dingare C, Cao D, Yang J, Sozen B, Steventon B. Mannose controls mesoderm specification and symmetry breaking in mouse gastruloids. Developmental Cell 2024, 59: 1523-1537.e6. PMID: 38636516, DOI: 10.1016/j.devcel.2024.03.031.Peer-Reviewed Original ResearchConceptsMesoderm specificationFeatures of embryonic developmentWnt pathway regulationEarly mesoderm developmentProtein glycosylationPathway regulationProteomic analysisIntracellular recyclingMesoderm developmentEmbryonic developmentGlycolytic intermediatesMannoseGlucose transportCompetitive inhibitorGlycosylationGlucose removal
2023
CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability
Deniz E, Pasha M, Guerra M, Viviano S, Ji W, Konstantino M, Jeffries L, Lakhani S, Medne L, Skraban C, Krantz I, Khokha M. CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability. Developmental Biology 2023, 499: 75-88. PMID: 37172641, PMCID: PMC10373286, DOI: 10.1016/j.ydbio.2023.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningCiliaHeart Defects, CongenitalHeterotaxy SyndromeMutation, MissensePhenotypeXenopusXenopus ProteinsConceptsLeft-right organizerCilia stabilityLeft-right patterningCongenital heart disease genesApical surfaceCell apical surfaceLive confocal imagingLeftward fluid flowHeart disease genesRecessive missense mutationLethal birth defectMotile monociliaProtein familyEarly embryogenesisMulticiliated cellsCiliary axonemeDisease genesFrog embryosGenetic underpinningsWhole-exome sequencingMissense mutationsConfocal imagingEmbryosCiliaCongenital heart diseaseCilia function as calcium-mediated mechanosensors that instruct left-right asymmetry
Djenoune L, Mahamdeh M, Truong T, Nguyen C, Fraser S, Brueckner M, Howard J, Yuan S. Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry. Science 2023, 379: 71-78. PMID: 36603098, PMCID: PMC9939240, DOI: 10.1126/science.abq7317.Peer-Reviewed Original Research
2021
Human embryo polarization requires PLC signaling to mediate trophectoderm specification
Zhu M, Shahbazi M, Martin A, Zhang C, Sozen B, Borsos M, Mandelbaum RS, Paulson RJ, Mole MA, Esbert M, Titus S, Scott RT, Campbell A, Fishel S, Gradinaru V, Zhao H, Wu K, Chen ZJ, Seli E, de los Santos MJ, Goetz M. Human embryo polarization requires PLC signaling to mediate trophectoderm specification. ELife 2021, 10: e65068. PMID: 34569938, PMCID: PMC8514238, DOI: 10.7554/elife.65068.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdultBody PatterningCell DifferentiationCell LineageCell PolarityEmbryo Culture TechniquesEmbryo, MammalianFemaleGATA3 Transcription FactorGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicHumansPhosphoinositide Phospholipase CPhospholipase C betaPregnancySignal TransductionTime FactorsYoung AdultConceptsApical domain formationInner cell massEmbryo polarizationPhospholipase CFirst lineage segregationApico-basal polarizationEight-cell stageLineage segregationMammalian developmentTrophectoderm specificationTE fateApical enrichmentApical accumulationDistinct lineagesApical domainApolar cellsPar complexPolarized cellsRNA interferenceMolecular mechanismsF-actinHuman embryosCell stageEmbryosDomain formationAnalysis of lamprey meis genes reveals that conserved inputs from Hox, Meis and Pbx proteins control their expression in the hindbrain and neural tube
Parker H, De Kumar B, Pushel I, Bronner M, Krumlauf R. Analysis of lamprey meis genes reveals that conserved inputs from Hox, Meis and Pbx proteins control their expression in the hindbrain and neural tube. Developmental Biology 2021, 479: 61-76. PMID: 34310923, DOI: 10.1016/j.ydbio.2021.07.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBody PatterningConserved SequenceEnhancer Elements, GeneticGene ExpressionGene Expression Regulation, DevelopmentalGenes, HomeoboxHomeodomain ProteinsLampreysMyeloid Ecotropic Viral Integration Site 1 ProteinNeural CrestNeural TubePre-B-Cell Leukemia Transcription Factor 1RhombencephalonTranscription FactorsConceptsMeis genesTALE proteinsDivergence of jawedSea lamprey genomeEvolution of vertebratesNeural crest cellsLamprey genomeTALE factorsPattern of expressionPbx proteinsJawed vertebratesVertebrate evolutionDeep ancestryJawless vertebratesLamprey embryosRhombomeric domainsTransgenic reporterNeural enhancerSimilar relative positionsRegulatory interactionsPharyngeal archesReporter expressionHead developmentCrest cellsSequence alignmentRole of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates
Brady MV, Vaccarino FM. Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates. Cells 2021, 10: 914. PMID: 33923415, PMCID: PMC8073580, DOI: 10.3390/cells10040914.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsBody PatterningHedgehog ProteinsHumansModels, BiologicalPluripotent Stem CellsProsencephalonSignal TransductionConceptsSonic hedgehogHuman neurodevelopmentHuman pluripotent cellsDiverse cellular compositionRole of SHHMaster regulatorPluripotent cellsCellular phenotypesVentral identityNeural organoidsExpression gradientsOrganoid systemsDisease modelingVitro systemPathway activationModel systemCellular compositionOrganoidsHuman developmentQuestions scientistsHedgehogBiologyDynamics of hunchback translation in real-time and at single-mRNA resolution in the Drosophila embryo
Vinter DJ, Hoppe C, Minchington TG, Sutcliffe C, Ashe HL. Dynamics of hunchback translation in real-time and at single-mRNA resolution in the Drosophila embryo. Development 2021, 148: dev196121. PMID: 33722899, PMCID: PMC8077512, DOI: 10.1242/dev.196121.Peer-Reviewed Original ResearchConceptsSingle mRNA resolutionDrosophila embryosHb mRNAMRNA translationAnterior-posterior patterningLive embryosSingle-molecule imagingTissue culture cellsTranslational repressionDevelopmental patterningSpatiotemporal regulationTranslational regulationExpression domainsSunTag systemTranscription factorsExpression boundariesTranslation dynamicsEmbryosCulture cellsMRNARepressionRegulationPatterningDrosophilaTranslation
2020
The dynamics of morphogenesis in stem cell-based embryology: Novel insights for symmetry breaking
Sozen B, Cornwall-Scoones J, Zernicka-Goetz M. The dynamics of morphogenesis in stem cell-based embryology: Novel insights for symmetry breaking. Developmental Biology 2020, 474: 82-90. PMID: 33333067, PMCID: PMC8259461, DOI: 10.1016/j.ydbio.2020.12.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningEmbryo, MammalianEmbryonic DevelopmentHumansMiceMorphogenesisSignal TransductionStem CellsConceptsSignaling gradientsMorphogen signaling gradientsAnteroposterior axis specificationMammalian embryosBody planAxis specificationSymmetry breakingModel of embryogenesisEmbryonic symmetryEmbryonic cellsPatterns in vivoMolecular processesAdult organismBiochemical mechanismsDynamics of morphogenesisEmbryogenesisIn vitro modelEmbryosModel systemIn vitroCritical processCellsMorphogenMorphogenesisStem cellsModulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
Hoppe C, Bowles JR, Minchington TG, Sutcliffe C, Upadhyai P, Rattray M, Ashe HL. Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo. Developmental Cell 2020, 54: 727-741.e7. PMID: 32758422, PMCID: PMC7527239, DOI: 10.1016/j.devcel.2020.07.007.Peer-Reviewed Original ResearchConceptsDrosophila embryosCell fate decisionsMorphogen gradient interpretationTarget gene transcriptsSingle-cell resolutionBMP gradientMRNA outputAxis patterningCell fateExpression domainsTranscriptional responsePromoter sequencesGene transcriptsProtein gradientGradient interpretationBurst kineticsBMPEmbryosEnhancerClassic exampleCellsActivation rateMorphogensTranscriptsGeneral featuresShootin‐1 is required for nervous system development in zebrafish
Emerson S, Stergas H, Bupp‐Chickering S, Ebert A. Shootin‐1 is required for nervous system development in zebrafish. Developmental Dynamics 2020, 249: 1285-1295. PMID: 32406957, DOI: 10.1002/dvdy.194.Peer-Reviewed Original ResearchConceptsNervous system developmentLoss of repressionShootin-1Peripheral nervous systemRepulsive axon guidance cuesDownstream signaling mechanismsPhenotypic consequencesNervous systemAxon guidance cuesNeuronal polarityPatterning defectsMicroarray screeningRetinal pigment epitheliumCell migrationGuidance cuesSignaling mechanismsFunctional roleImpaired migrationPLXNA2RepressionPigment epitheliumOptic vesiclePathfinding errorsZebrafishRegulationGeneration of Regionally Specified Human Brain Organoids Resembling Thalamus Development
Xiang Y, Cakir B, Park IH. Generation of Regionally Specified Human Brain Organoids Resembling Thalamus Development. STAR Protocols 2020, 1: 100001. PMID: 33103124, PMCID: PMC7580078, DOI: 10.1016/j.xpro.2019.100001.Peer-Reviewed Original ResearchMeSH KeywordsBody PatterningCells, CulturedHumansModels, BiologicalOrganoidsPluripotent Stem CellsThalamus
2019
Polycomb Repressive Complex 1 Controls Maintenance of Fungiform Papillae by Repressing Sonic Hedgehog Expression
Bar C, Cohen I, Zhao D, Pothula V, Litskevitch A, Koseki H, Zheng D, Ezhkova E. Polycomb Repressive Complex 1 Controls Maintenance of Fungiform Papillae by Repressing Sonic Hedgehog Expression. Cell Reports 2019, 28: 257-266.e5. PMID: 31269445, PMCID: PMC6921245, DOI: 10.1016/j.celrep.2019.06.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningCell CycleChromatin ImmunoprecipitationChromatin Immunoprecipitation SequencingCyclin-Dependent Kinase Inhibitor p16Epigenesis, GeneticEpitheliumGene Expression Regulation, DevelopmentalGene OntologyHedgehog ProteinsMiceMice, KnockoutMicroscopy, Electron, ScanningPolycomb Repressive Complex 1Polycomb Repressive Complex 2RNA-SeqSignal TransductionTaste BudsTongueConceptsGene expressionPolycomb Repressive Complex 1Spatial gene expression patternsRepressive Complex 1Gene expression patternsCell gene expressionChromatin regulatorsTissue patterningSonic hedgehog expressionEpigenetic regulationNiche structureExpression patternsCell genesEpithelial progenitorsHedgehog expressionShhEctopic ShhTaste cellsPapilla structuresTissue patternsExpressionCellsPatterningProper maintenanceComplexes 1Organization 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 modeling
2018
Spine Patterning Is Guided by Segmentation of the Notochord Sheath
Wopat S, Bagwell J, Sumigray KD, Dickson AL, Huitema LFA, Poss KD, Schulte-Merker S, Bagnat M. Spine Patterning Is Guided by Segmentation of the Notochord Sheath. Cell Reports 2018, 22: 2026-2038. PMID: 29466731, PMCID: PMC5860813, DOI: 10.1016/j.celrep.2018.01.084.Peer-Reviewed Original ResearchConceptsNotochord sheathTissue-specific manipulationActivation of NotchZebrafish notochordCentrum formationVertebral patterningOuter epithelial cell layerSheath cellsSegmentation defectsAxial structuresEpithelial cell layerNotochordPatterningIVD areaZebrafish spineDomainCell layerNotchCentraOsteoblastsSheathCellsActivationHOXA5 protein expression and genetic fate mapping show lineage restriction in the developing musculoskeletal system
Holzman MA, Bergmann JM, Feldman M, Landry-Truchon K, Jeannotte L, Mansfield JH. HOXA5 protein expression and genetic fate mapping show lineage restriction in the developing musculoskeletal system. The International Journal Of Developmental Biology 2018, 62: 785-796. PMID: 30604848, PMCID: PMC8783609, DOI: 10.1387/ijdb.180214jm.Peer-Reviewed Original ResearchConceptsLateral plate mesodermHOXA5 expressionSkeletal patterningPlate mesodermNon-cell autonomous functionCell-autonomous roleProtein expressionSatellite cell lineageLineage restrictionGenetic lineagesEmbryonic cellsCell lineagesLateral sclerotomeTissue specificitySomite stageSkeletal developmentLineagesAutonomous roleDirect roleMusculoskeletal morphologyTissue typesMesodermHOXA5SomitesAutonomous functions
2017
Patterned 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 ResearchMeSH KeywordsAnimalsBody PatterningCell MovementComputer SimulationModels, BiologicalSpineTailZebrafishZebrafish ProteinsPolarization and migration in the zebrafish posterior lateral line system
Knutsdottir H, Zmurchok C, Bhaskar D, Palsson E, Nogare D, Chitnis A, Edelstein-Keshet L. Polarization and migration in the zebrafish posterior lateral line system. PLOS Computational Biology 2017, 13: e1005451. PMID: 28369079, PMCID: PMC5393887, DOI: 10.1371/journal.pcbi.1005451.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBody PatterningCell MovementCell PolarityComputational BiologyModels, BiologicalZebrafishConceptsPosterior lateral line primordiumZebrafish posterior lateral line systemCell-cell adhesionLateral line primordiumCollective cell migrationPosterior lateral line systemCell-based simulationsMutant phenotypeZebrafish embryosCell divisionFGF ligandsLateral line systemCell migrationTrailing cellsSensory structuresObserved motilityChemotaxisCellsImportant roleCXCL12aPrimordiaAdhesionEmbryosMigrationPhenotype
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