Desert Hedgehog-Primary Cilia Cross Talk Shapes Mitral Valve Tissue by Organizing Smooth Muscle Actin
| dc.rights.license | open | en_US |
| dc.contributor.author | FULMER, Diana | |
| dc.contributor.author | TOOMER, Katelynn A. | |
| dc.contributor.author | GLOVER, Janiece | |
| dc.contributor.author | GUO, Lilong | |
| dc.contributor.author | MOORE, Kelsey | |
| dc.contributor.author | MOORE, Reece | |
| dc.contributor.author | STAIRLEY, Rebecca | |
| dc.contributor.author | GENSEMER, Cortney | |
| dc.contributor.author | ABROL, Sameer | |
| dc.contributor.author | RUMPH, Mary Kate | |
| dc.contributor.author | EMETU, Faith | |
| dc.contributor.author | LIPSCHUTZ, Joshua | |
| dc.contributor.author | MCDOWELL, Colin | |
| dc.contributor.author | BIAN, Justin | |
| dc.contributor.author | WANG, Christina | |
| dc.contributor.author | BECK, Tyler | |
| dc.contributor.author | WESSELS, Andy | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | RENAULT, Marie-Ange | |
| dc.contributor.author | NORRIS, Russell | |
| dc.date.accessioned | 2020-10-19T14:39:26Z | |
| dc.date.available | 2020-10-19T14:39:26Z | |
| dc.date.issued | 2020 | |
| dc.identifier.issn | 1095-564X | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/11438 | |
| dc.description.abstractEn | Non-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.iso | EN | en_US |
| dc.subject.en | Actins | |
| dc.subject.en | Animals | |
| dc.subject.en | Cilia | |
| dc.subject.en | Extracellular Matrix | |
| dc.subject.en | Heart Valve Diseases | |
| dc.subject.en | Hedgehog Proteins | |
| dc.subject.en | Mice | |
| dc.subject.en | Mitral Valve | |
| dc.subject.en | Mitral Valve Prolapse | |
| dc.subject.en | Muscle | |
| dc.subject.en | Smooth | |
| dc.subject.en | Myocytes | |
| dc.subject.en | Smooth Muscle | |
| dc.subject.en | Neuropeptides | |
| dc.subject.en | Phenotype | |
| dc.subject.en | Signal Transduction | |
| dc.subject.en | Transcription Factors | |
| dc.subject.en | rac1 GTP-Binding Protein | |
| dc.title.en | Desert Hedgehog-Primary Cilia Cross Talk Shapes Mitral Valve Tissue by Organizing Smooth Muscle Actin | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.ydbio.2020.03.003 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| bordeaux.journal | Developmental Biology | en_US |
| bordeaux.hal.laboratories | Biologie des maladies cardiovasculaires - U1034 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.export | false | |
| bordeaux.COinS | ctx_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 |
