2025
Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions
Mao S, Song R, Jin S, Pang S, Jovanovic A, Zimmerman A, Li P, Wu X, Wendland M, Lin K, Chen W, Choksi S, Chen G, Holtzman M, Reiter J, Wan Y, Xuan Z, Xiang Y, Xu C, Upadhyayula S, Hess H, He L. Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions. Cell Reports 2025, 44: 115383. PMID: 40057957, DOI: 10.1016/j.celrep.2025.115383.Peer-Reviewed Original ResearchConceptsCSF productionChoroid plexusCerebrospinal fluidSonic hedgehog signalingWater channel AQP1Increased CSF productionHedgehog signalingChoroid plexus functionMotile ciliaMulticiliaSensory ciliaShh signalingNeonatal hydrocephalusSonic hedgehogCiliary lengthRegulate CSF productionSignal intensityCiliary ultrastructureChoroidEpithelial monolayersAQP1Developmental dynamicsCiliaATP1A2PlexusCACNA1G, 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 development
2024
Cilia structure and intraflagellar transport differentially regulate sensory response dynamics within and between C. elegans chemosensory neurons
Philbrook A, O’Donnell M, Grunenkovaite L, Sengupta P. Cilia structure and intraflagellar transport differentially regulate sensory response dynamics within and between C. elegans chemosensory neurons. PLOS Biology 2024, 22: e3002892. PMID: 39591402, PMCID: PMC11593760, DOI: 10.1371/journal.pbio.3002892.Peer-Reviewed Original ResearchConceptsIntraflagellar transportOrganization of signaling moleculesASH nociceptive neuronsAWA olfactory neuronsCiliary traffickingNociceptive neuronsCilia baseOlfactory neuronsCaenorhabditis elegansOdor responsesSignaling proteinsCilia organizationSensory neuronsCilium structurePrimary ciliaCilia structureSignaling moleculesAcute inhibitionSegregation of receptorsRegulation of responsesChemosensory neuronsNeuron typesCilium lengthNeuronal responsesEctopic branchingStructure, interaction and nervous connectivity of beta cell primary cilia
Müller A, Klena N, Pang S, Garcia L, Topcheva O, Aurrecoechea Duran S, Sulaymankhil D, Seliskar M, Mziaut H, Schöniger E, Friedland D, Kipke N, Kretschmar S, Münster C, Weitz J, Distler M, Kurth T, Schmidt D, Hess H, Xu C, Pigino G, Solimena M. Structure, interaction and nervous connectivity of beta cell primary cilia. Nature Communications 2024, 15: 9168. PMID: 39448638, PMCID: PMC11502866, DOI: 10.1038/s41467-024-53348-5.Peer-Reviewed Original ResearchConceptsPrimary ciliaCell's primary ciliumNon-islet cellsPancreatic beta cellsCiliary pocketSensory organellesAxonemal organizationMotility componentsExtrinsic signalsStructural basisBeta cellsCiliaCell typesExpansion microscopyParacrine signalingIslet innervationCellsIsletsBetaAxonemeOrganellesSignalThree-dimensional reconstructionInteractionCC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow
Kim A, Sakin I, Viviano S, Tuncel G, Aguilera S, Goles G, Jeffries L, Ji W, Lakhani S, Kose C, Silan F, Oner S, Kaplan O, Group M, Ergoren M, Mishra-Gorur K, Gunel M, Sag S, Temel S, Deniz E. CC2D1A causes ciliopathy, intellectual disability, heterotaxy, renal dysplasia, and abnormal CSF flow. Life Science Alliance 2024, 7: e202402708. PMID: 39168639, PMCID: PMC11339347, DOI: 10.26508/lsa.202402708.Peer-Reviewed Original ResearchConceptsDevelopmental disabilitiesIntellectual disabilityPatient-derived fibroblastsMidbrain regionsBrain developmentDefective ciliogenesisCSF circulationDisabilityCSF flowAbnormal CSF flowNervous system developmentMutant tadpolesCiliated tissuesMultiple model systemsVariant functionPronephric ductUnrelated familiesCC2D1AExpression patternsCiliogenesisRenal dysplasiaLeft-right organizerFunctional analysisDisease mechanismsBrainPathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics
DeSpenza T, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina M, Desmet N, Dang H, Fields J, Nelson-Williams C, Zhang J, Mekbib K, Dennis E, Mehta N, Duy P, Shimelis H, Walsh L, Marlier A, Deniz E, Lake E, Constable R, Hoffman E, Lifton R, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper S, Jin S, Kahle K, Luikart B. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314702121. PMID: 38916997, PMCID: PMC11228466, DOI: 10.1073/pnas.2314702121.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventriculomegalyPathogenic variantsPrefrontal pyramidal neuronsGenetic subsets of patientsDevelopment of ventriculomegalyRadial gliaSubsets of patientsHigh-frequency firingNeuronal connectivityHeterozygous germline variantsAutism spectrum disorderVentricular-subventricular zoneMicrotubule dynamicsImpaired spermatogenesisCSF shuntingExcitatory driveMicrotubule-severing ATPasePyramidal neuronsDisrupt neuronal connectivityGermline variantsVentriculomegalyCSF homeostasisDisrupt microtubule dynamicsPlanar cell polarityLoss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice
Kang R, Kim K, Jung Y, Choi S, Lee C, Im G, Shin M, Ryu K, Choi S, Yang E, Shin W, Lee S, Lee S, Papadopoulos Z, Ahn J, Koh G, Kipnis J, Kang H, Kim H, Cho W, Park S, Kim S, Kim E. Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice. PLOS Biology 2024, 22: e3002596. PMID: 38718086, PMCID: PMC11104772, DOI: 10.1371/journal.pbio.3002596.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderBehavioral phenotypesASD-relatedSocial communication deficitsAutism-related phenotypesEnlarged lateral ventriclesProgressive ventricular enlargementCommunication deficitsSpectrum disorderSynaptic deficitsEnlargement of brain ventriclesTranscriptomic changesMicrotubule-regulatory proteinsGenes down-regulatedBrain ventriclesVentricular enlargementLateral ventricleDeficitsHippocampal neuronsMotile ciliaKATNAL2Potential treatmentDown-regulationCiliary functionEpendymal cellsGlis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease
Zhang C, Rehman M, Tian X, Pei S, Gu J, Bell T, Dong K, Tham M, Cai Y, Wei Z, Behrens F, Jetten A, Zhao H, Lek M, Somlo S. Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease. Nature Communications 2024, 15: 3698. PMID: 38693102, PMCID: PMC11063051, DOI: 10.1038/s41467-024-48025-6.Peer-Reviewed Original ResearchConceptsMouse models of autosomal dominant polycystic kidney diseaseModel of autosomal dominant polycystic kidney diseasePolycystin signalingAutosomal dominant polycystic kidney diseasePolycystin-1Polycystic kidney diseaseTreat autosomal dominant polycystic kidney diseaseGlis2Primary ciliaKidney tubule cellsSignaling pathwayMouse modelDominant polycystic kidney diseasePotential therapeutic targetTranslatomeAntisense oligonucleotidesKidney diseasePolycystinMouse kidneyFunctional effectorsCyst formationTherapeutic targetInactivationFunctional targetPharmacological targets
2023
Cryo-EM reveals how the mastigoneme assembles and responds to environmental signal changes
Wang Y, Yang J, Hu F, Yang Y, Huang K, Zhang K. Cryo-EM reveals how the mastigoneme assembles and responds to environmental signal changes. Journal Of Cell Biology 2023, 222: e202301066. PMID: 37882754, PMCID: PMC10602792, DOI: 10.1083/jcb.202301066.Peer-Reviewed Original ResearchConceptsSingle-particle cryo-electron microscopy structureCryo-electron microscopy structureNon-polar filamentsImmunoglobulin-like domainsDistal regionPolyproline II helixMicroscopy structureChlamydomonas reinhardtiiFlagellar motilityVaried environmental conditionsCryo-EMCell swimmingMotility controlEnvironmental responsesDisulfide bondsEnvironmental conditionsSushi domainMastigonemesThread-like structuresRedox shiftSignal sensingPotential roleProtistsReinhardtiiMST1Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome
Bruel A, Ganga A, Nosková L, Valenzuela I, Martinovic J, Duffourd Y, Zikánová M, Majer F, Kmoch S, Mohler M, Sun J, Sweeney L, Martínez-Gil N, Thauvin-Robinet C, Breslow D. Pathogenic RAB34 variants impair primary cilium assembly and cause a novel oral-facial-digital syndrome. Human Molecular Genetics 2023, 32: 2822-2831. PMID: 37384395, PMCID: PMC10481091, DOI: 10.1093/hmg/ddad109.Peer-Reviewed Original ResearchConceptsCilia assemblyCiliary membrane formationIntracellular ciliogenesis pathwayPrimary cilia assemblyBi-allelic missense variantsRab proteinsRab GTPaseCiliary proteinsSmall GTPaseNascent ciliaMother centriolePrimary ciliaC-terminusProtein productsPathogenic variantsRab34Cell typesFunctional impactMissense variantsGTPaseStrong lossCiliogenesisSignificant defectsGenesKey mediatorCFAP45, 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 ResearchConceptsLeft-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 diseaseInactivation of Invs/Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse
Li Y, Xu W, Makova S, Brueckner M, Sun Z. Inactivation of Invs/Nphp2 in renal epithelial cells drives infantile nephronophthisis like phenotypes in mouse. ELife 2023, 12: e82395. PMID: 36920028, PMCID: PMC10154023, DOI: 10.7554/elife.82395.Peer-Reviewed Original ResearchConceptsFlox/Valproic acidRenal fibrosisCyst formationEnd-stage renal diseaseMutant miceHistone deacetylase inhibitor valproic acidKidney function declineStage renal diseaseCell proliferationInhibitor valproic acidEpithelial-stromal crosstalkKnockout mouse modelRenal cyst formationCyst burdenRenal diseaseFunction declineInterstitial fibrosisDisease progressionStromal fibrosisTargeted therapyInfantile nephronophthisisMouse modelMyofibroblast activationRenal epithelial cellsCilia 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 ResearchHYDIN Variants Are a Common Cause of Primary Ciliary Dyskinesia in French Canadians.
Shapiro A, Sillon G, D'Agostino D, Baret L, López-Giráldez F, Mane S, Leigh M, Davis S, Knowles M, Zariwala M. HYDIN Variants Are a Common Cause of Primary Ciliary Dyskinesia in French Canadians. Annals Of The American Thoracic Society 2023, 20: 140-144. PMID: 36112114, PMCID: PMC9819264, DOI: 10.1513/annalsats.202203-253rl.Peer-Reviewed Original Research
2022
A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility
Sheu SH, Upadhyayula S, Dupuy V, Pang S, Deng F, Wan J, Walpita D, Pasolli HA, Houser J, Sanchez-Martinez S, Brauchi SE, Banala S, Freeman M, Xu CS, Kirchhausen T, Hess HF, Lavis L, Li Y, Chaumont-Dubel S, Clapham DE. A serotonergic axon-cilium synapse drives nuclear signaling to alter chromatin accessibility. Cell 2022, 185: 3390-3407.e18. PMID: 36055200, PMCID: PMC9789380, DOI: 10.1016/j.cell.2022.07.026.Peer-Reviewed Original ResearchConceptsCA1 pyramidal neuronsChromatin accessibilityPyramidal neuronsSerotonergic axonsEpigenetic statePrimary ciliaHippocampal CA1 pyramidal neuronsChemogenetic stimulationSerotonin receptorsNuclear actinReceptor 6Histone acetylationAxonsChemical synapsesIntercellular communicationRhoA pathwaySynapseNeuronsCiliaSynapsesStimulationPathwayNeurotransmissionReceptorsPolycystin-2 in the Endoplasmic Reticulum: Bending Ideas about the Role of the Cilium
Caplan MJ. Polycystin-2 in the Endoplasmic Reticulum: Bending Ideas about the Role of the Cilium. Journal Of The American Society Of Nephrology 2022, 33: 1433-1434. PMID: 35906088, PMCID: PMC9342637, DOI: 10.1681/asn.2022050557.Peer-Reviewed Original ResearchCryo-EM structure of an active central apparatus
Han L, Rao Q, Yang R, Wang Y, Chai P, Xiong Y, Zhang K. Cryo-EM structure of an active central apparatus. Nature Structural & Molecular Biology 2022, 29: 472-482. PMID: 35578022, PMCID: PMC9113940, DOI: 10.1038/s41594-022-00769-9.Peer-Reviewed Original ResearchConceptsCentral apparatusDiverse cellular activitiesKinesin-like proteinCryo-EM structureArmadillo repeat proteinsCryo-electron microscopyHigh-resolution structuresEukaryotic speciesProtein subunitsMotile ciliaBridge proteinsPair of microtubulesRegulatory roleCellular activitiesProteinDynamic conformational behaviorCiliary motilityCiliaCiliary beatingStructural frameworkConformational behaviorSubunitsMicrotubulesRegulatorSpeciesThe role of SPAG1 in the assembly of axonemal dyneins in human airway epithelia
Smith AJ, Bustamante-Marin XM, Yin W, Sears PR, Herring LE, Dicheva NN, López-Giráldez F, Mane S, Tarran R, Leigh MW, Knowles MR, Zariwala MA, Ostrowski LE. The role of SPAG1 in the assembly of axonemal dyneins in human airway epithelia. Journal Of Cell Science 2022, 135 PMID: 35178554, PMCID: PMC8995097, DOI: 10.1242/jcs.259512.Peer-Reviewed Original Research
2021
A change of heart: new roles for cilia in cardiac development and disease
Djenoune L, Berg K, Brueckner M, Yuan S. A change of heart: new roles for cilia in cardiac development and disease. Nature Reviews Cardiology 2021, 19: 211-227. PMID: 34862511, PMCID: PMC10161238, DOI: 10.1038/s41569-021-00635-z.Peer-Reviewed Original ResearchConceptsCongenital heart diseaseHeart diseaseCardiac valve disordersAortic valve diseaseMitral valve prolapseCardiac developmentValve diseaseValve prolapseMyocardial fibrosisValve disordersCardiac abnormalitiesPresence of ciliaCardiac fibroblastsCilia functionContractile forceDiseaseFunction contributesLines of evidenceDefective primary ciliaPotential roleHeart regenerationBroader roleHeartDisordersLatest findingsRab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway
Ganga AK, Kennedy MC, Oguchi ME, Gray S, Oliver KE, Knight TA, De La Cruz EM, Homma Y, Fukuda M, Breslow DK. Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway. Current Biology 2021, 31: 2895-2905.e7. PMID: 33989527, PMCID: PMC8282722, DOI: 10.1016/j.cub.2021.04.075.Peer-Reviewed Original ResearchConceptsIntracellular pathwaysCiliary membrane biogenesisCiliary membrane formationIntracellular ciliogenesis pathwayMDCK cellsPolarized MDCK cellsDistinct molecular requirementsPrimary cilia formExtracellular pathwaysTissue-specific mannerCiliary pocketGTPase domainMembrane biogenesisDistinct functional propertiesCiliary vesiclesAssembly intermediatesCilia formSignal transductionGTP bindingMother centriolePrimary ciliaCiliogenesisDivergent residuesIntracellular ciliaRab34
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