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Desert Hedgehog-Primary Cilia Cross Talk Shapes Mitral Valve Tissue by Organizing Smooth Muscle Actin

dc.rights.licenseopenen_US
dc.contributor.authorFULMER, Diana
dc.contributor.authorTOOMER, Katelynn A.
dc.contributor.authorGLOVER, Janiece
dc.contributor.authorGUO, Lilong
dc.contributor.authorMOORE, Kelsey
dc.contributor.authorMOORE, Reece
dc.contributor.authorSTAIRLEY, Rebecca
dc.contributor.authorGENSEMER, Cortney
dc.contributor.authorABROL, Sameer
dc.contributor.authorRUMPH, Mary Kate
dc.contributor.authorEMETU, Faith
dc.contributor.authorLIPSCHUTZ, Joshua
dc.contributor.authorMCDOWELL, Colin
dc.contributor.authorBIAN, Justin
dc.contributor.authorWANG, Christina
dc.contributor.authorBECK, Tyler
dc.contributor.authorWESSELS, Andy
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorRENAULT, Marie-Ange
dc.contributor.authorNORRIS, Russell
dc.date.accessioned2020-10-19T14:39:26Z
dc.date.available2020-10-19T14:39:26Z
dc.date.issued2020
dc.identifier.issn1095-564Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/11438
dc.description.abstractEnNon-syndromic mitral valve prolapse (MVP) is the most common heart valve disease affecting 2.4% of the population. Recent studies have identified genetic defects in primary cilia as causative to MVP, although the mechanism of their action is currently unknown. Using a series of gene inactivation approaches, we define a paracrine mechanism by which endocardially-expressed Desert Hedgehog (DHH) activates primary cilia signaling on neighboring valve interstitial cells. High-resolution imaging and functional assays show that DHH de-represses smoothened at the primary cilia, resulting in kinase activation of RAC1 through the RAC1-GEF, TIAM1. Activation of this non-canonical hedgehog pathway stimulates α-smooth actin organization and ECM remodeling. Genetic or pharmacological perturbation of this pathway results in enlarged valves that progress to a myxomatous phenotype, similar to valves seen in MVP patients. These data identify a potential molecular origin for MVP as well as establish a paracrine DHH-primary cilium cross-talk mechanism that is likely applicable across developmental tissue types.
dc.language.isoENen_US
dc.subject.enActins
dc.subject.enAnimals
dc.subject.enCilia
dc.subject.enExtracellular Matrix
dc.subject.enHeart Valve Diseases
dc.subject.enHedgehog Proteins
dc.subject.enMice
dc.subject.enMitral Valve
dc.subject.enMitral Valve Prolapse
dc.subject.enMuscle
dc.subject.enSmooth
dc.subject.enMyocytes
dc.subject.enSmooth Muscle
dc.subject.enNeuropeptides
dc.subject.enPhenotype
dc.subject.enSignal Transduction
dc.subject.enTranscription Factors
dc.subject.enrac1 GTP-Binding Protein
dc.title.enDesert Hedgehog-Primary Cilia Cross Talk Shapes Mitral Valve Tissue by Organizing Smooth Muscle Actin
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.ydbio.2020.03.003en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.journalDevelopmental Biologyen_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Developmental%20Biology&rft.date=2020&rft.eissn=1095-564X&rft.issn=1095-564X&rft.au=FULMER,%20Diana&TOOMER,%20Katelynn%20A.&GLOVER,%20Janiece&GUO,%20Lilong&MOORE,%20Kelsey&rft.genre=article


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