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Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates.

dc.rights.licenseopenen_US
dc.contributor.authorSZENKER-RAVI, Emmanuelle
dc.contributor.authorOTT, Tim
dc.contributor.authorKHATOO, Muznah
dc.contributor.authorMOREAU DE BELLAING, Anne
dc.contributor.authorGOH, Wei Xuan
dc.contributor.authorCHONG, Yan Ling
dc.contributor.authorBECKERS, Anja
dc.contributor.authorKANNESAN, Darshini
dc.contributor.authorLOUVEL, Guillaume
dc.contributor.authorANUJAN, Priyanka
dc.contributor.authorRAVI, Vydianathan
dc.contributor.authorBONNARD, Carine
dc.contributor.authorMOUTTON, Sebastien
dc.contributor.authorSCHOEN, Patric
dc.contributor.authorFRADIN, Melanie
dc.contributor.authorCOLIN, Estelle
dc.contributor.authorMEGARBANE, Andre
dc.contributor.authorDAOU, Linda
dc.contributor.authorCHEHAB, Ghassan
dc.contributor.authorDI FILIPPO, Sylvie
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorROORYCK, Caroline
dc.contributor.authorDELEUZE, Jean-François
dc.contributor.authorBOLAND, Anne
dc.contributor.authorARRIBARD, Nicolas
dc.contributor.authorEKER, Rukiye
dc.contributor.authorTOHARI, Sumanty
dc.contributor.authorNG, Alvin Yu-Jin
dc.contributor.authorRIO, Marlene
dc.contributor.authorLIM, Chun Teck
dc.contributor.authorEISENHABER, Birgit
dc.contributor.authorEISENHABER, Frank
dc.contributor.authorVENKATESH, Byrappa
dc.contributor.authorAMIEL, Jeanne
dc.contributor.authorCROLLIUS, Hugues Roest
dc.contributor.authorGORDON, Christopher T
dc.contributor.authorGOSSLER, Achim
dc.contributor.authorROY, Sudipto
dc.contributor.authorATTIE-BITACH, Tania
dc.contributor.authorBLUM, Martin
dc.contributor.authorBOUVAGNET, Patrice
dc.contributor.authorREVERSADE, Bruno
dc.date.accessioned2023-11-09T16:21:04Z
dc.date.available2023-11-09T16:21:04Z
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/184703
dc.description.abstractEnThe vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans.
dc.language.isoENen_US
dc.subject.enAnimals
dc.subject.enHumans
dc.subject.enBiological Evolution
dc.subject.enBody Patterning
dc.subject.enCilia
dc.subject.enGene Regulatory Networks
dc.subject.enLoss of Function Mutation
dc.subject.enMetalloproteases
dc.subject.enProteins
dc.subject.enVertebrates
dc.title.enDiscovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates.
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1038/s41588-021-00970-4en_US
dc.subject.halSciences du Vivant [q-bio]en_US
dc.identifier.pubmed34903892en_US
bordeaux.journalNature Geneticsen_US
bordeaux.page62-72en_US
bordeaux.volume54en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.import.sourcepubmed
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.subtypePrepublication/Preprinten_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Genetics&rft.volume=54&rft.issue=1&rft.spage=62-72&rft.epage=62-72&rft.au=SZENKER-RAVI,%20Emmanuelle&OTT,%20Tim&KHATOO,%20Muznah&MOREAU%20DE%20BELLAING,%20Anne&GOH,%20Wei%20Xuan&rft.genre=preprint


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