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REVIEWTheintestinalepitheliumtuftcells:specificationandfunctionFranc¸oisGerbe•CatherineLegraverend•PhilippeJayReceived:23February2012/Revised:21March2012/Accepted:26March2012/Publishedonline:19April2012�TheAuthor(s)2012.ThisarticleispublishedwithopenaccessatSpringerlink.comAbstractTheintestinalepithelium,composedofatleastsevendifferentiatedcelltypes,representsanextraordinarymodeltounderstandthedetailsofmulti-lineagedifferen-tiation,aquestionthatishighlyrelevantindevelopmentalbiologyaswellasforclinicalapplications.Thisreviewfocusesonintestinalepithelialtuftcellsthathavebeenacknowledgedasaseparateentityformorethan60yearsbutwhosefunctionremainsamystery.Wediscusswhatiscurrentlyknownaboutthemolecularbasisoftuftcellfateanddifferentiationandwhyelucidatingtuftcellfunctionhasbeensodifficult.Finally,wesummarizethecurrenthypothesesontheirpotentialinvolvementindiseasesofthegastro-intestinaltract.KeywordsTuftcells�Brushcells�Intestinalepithelium�Atoh1�Celldifferentiation�Dclk1AbbreviationsAc-tubulinAcetylatedtubulinAtoh1Atonalhomolog1BrdU5-Bromo-20-deoxyuridineCFTRCysticfibrosistransmembraneconductanceregulatorhomologCK-18Cytokeratin18DCLK1Doublecortin-likekinase1DllDelta-likeF-actinFibrillaractinGfi1Growthfactorindependent1Gfi1bGrowthfactorindependent1bGIGastro-intestinalGIPGastricinhibitorypolypeptideGLP-1Glucagon-likepeptide1Hes1Hairyandenhancerofsplit1HpgdsHematopoieticprostaglandinDsynthaseKlf4Kruppel-likefactor4L-FABPFattyacid-bindingprotein1,liverLgr5Leucine-richrepeat-containingGprotein-coupledreceptor5Neurog3Neurogenin3nNOSNitricoxidesynthase1,neuronalPGD2ProstaglandinD2PLCb2PhospholipaseC,Beta2PLCc2PhospholipaseC,Gamma2PtgsProstaglandin-endoperoxidesynthaseSox9SRY-boxcontaininggene9SpdefSAMpointeddomaincontainingRtstranscriptionfactorT1RTastereceptor,type1Trpm5Transientreceptorpotentialcationchannel,subfamilyM,member5UEA-1Ulexeuropaeus-IlectinF.Gerbe�C.Legraverend�P.JayCNRSUMR5203,34094Montpellier,FranceF.Gerbe�C.Legraverend�P.JayINSERMU661,34094Montpellier,FranceF.Gerbe�C.Legraverend�P.JayMontpellierIUniversity,34094Montpellier,FranceF.Gerbe�C.Legraverend�P.JayMontpellierIIUniversity,34094Montpellier,FranceF.Gerbe�C.Legraverend�P.Jay(&)InstituteofFunctionalGenomics,141ruedelaCardonille,34094MontpellierCedex5,Francee-mail:philippe.jay@igf.cnrs.frCell.Mol.LifeSci.(2012)69:2907–2917DOI10.1007/s00018-012-0984-7CellularandMolecularLifeSciences123ScopeofthisreviewDuringthefivedecadesthatfollowedtheirdiscoveryintherattrachea[1]andinthemouseglandularstomach[2],thecharacterizationoftuftcellshasbeenhamperedbythelackofspecificmolecularmarkers,andnexttonothingwasknownabouttheirfunctions,butthisischanging.Severalmolecularmarkersthatallowtheirunambiguousidentifi-cationarenowavailable,andthesecanbeusedtocreatemouselinesinwhichreportersarespecificallyexpressedintuftcells.Theseadvancesaremakingtuftcellsamenabletothoroughanalysis,andweanticipatethatinsightsintotheirfunctionswillbeobtainedinthenearfuture.Theultra-structuralpropertiesoftuftcellshavealreadybeenthesubjectofexcellentreviews[3,4]andwillnotbedetailedhere.Wewillinsteadsummarizerecentlypublisheddataontheirproteinexpressionprofile,developmentaltiming,andlineagerelationshipstotheothercelltypescomposingtheintestinalepithelium.Wewillalsodiscusstheirpotentialimplicationinintestinaldiseases,and,relyingondatafromothero...