The level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling

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dc.contributor.authorXie, Mengcs
dc.contributor.authorKaiser, Markétacs
dc.contributor.authorGershtein, Yaakovcs
dc.contributor.authorSchnyder, Danielacs
dc.contributor.authorDeviatiiarov, Ruslancs
dc.contributor.authorGazizova, Guzelcs
dc.contributor.authorShagimardanova, Elenacs
dc.contributor.authorZikmund, Tomášcs
dc.contributor.authorKerckhofs, Greetcs
dc.contributor.authorIvashkin, Evgenycs
dc.contributor.authorBatkovskyte, Dominykacs
dc.contributor.authorNewton, Phillip T.cs
dc.contributor.authorAndersson, Olovcs
dc.contributor.authorFried, Kajcs
dc.contributor.authorGusev, Olegcs
dc.contributor.authorZeberg, Hugocs
dc.contributor.authorKaiser, Jozefcs
dc.contributor.authorAdameyko, Igorcs
dc.contributor.authorChagin, Andrei S.cs
dc.coverage.issueMarchcs
dc.coverage.volume15cs
dc.date.accessioned2024-10-14T09:04:07Z
dc.date.available2024-10-14T09:04:07Z
dc.date.issued2024-03-26cs
dc.description.abstractThe development of craniofacial skeletal structures is fascinatingly complex and elucidation of the underlying mechanisms will not only provide novel scientific insights, but also help develop more effective clinical approaches to the treatment and/or prevention of the numerous congenital craniofacial malformations. To this end, we performed a genome-wide analysis of RNA transcription from non-coding regulatory elements by CAGE-sequencing of the facial mesenchyme of human embryos and cross-checked the active enhancers thus identified against genes, identified by GWAS for the normal range human facial appearance. Among the identified active cis-enhancers, several belonged to the components of the PI3/AKT/mTORC1/autophagy pathway. To assess the functional role of this pathway, we manipulated it both genetically and pharmacologically in mice and zebrafish. These experiments revealed that mTORC1 signaling modulates craniofacial shaping at the stage of skeletal mesenchymal condensations, with subsequent fine-tuning during clonal intercalation. This ability of mTORC1 pathway to modulate facial shaping, along with its evolutionary conservation and ability to sense external stimuli, in particular dietary amino acids, indicate that the mTORC1 pathway may play a role in facial phenotypic plasticity. Indeed, the level of protein in the diet of pregnant female mice influenced the activity of mTORC1 in fetal craniofacial structures and altered the size of skeletogenic clones, thus exerting an impact on the local geometry and craniofacial shaping. Overall, our findings indicate that the mTORC1 signaling pathway is involved in the effect of environmental conditions on the shaping of craniofacial structures. Children's faces resemble their parents to various degrees. Here they show that the maternal diet affects the facial appearances of newborns and that inherited and adaptive mechanisms sculpturing facial bones are linked via dietary protein levels and the mTOR signaling pathway.en
dc.formattextcs
dc.format.extent1-15cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationNATURE COMMUNICATIONS. 2024, vol. 15, issue March, p. 1-15.en
dc.identifier.doi10.1038/s41467-024-46030-3cs
dc.identifier.issn2041-1723cs
dc.identifier.orcid0000-0002-5200-7365cs
dc.identifier.orcid0000-0003-2948-5198cs
dc.identifier.orcid0000-0002-7397-125Xcs
dc.identifier.other188572cs
dc.identifier.researcheridV-3696-2018cs
dc.identifier.researcheridG-9491-2014cs
dc.identifier.researcheridD-6800-2012cs
dc.identifier.scopus7402184758cs
dc.identifier.urihttps://hdl.handle.net/11012/249533
dc.language.isoencs
dc.publisherNATURE PORTFOLIOcs
dc.relation.ispartofNATURE COMMUNICATIONScs
dc.relation.urihttps://www.nature.com/articles/s41467-024-46030-3cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/2041-1723/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectmTORC1en
dc.subjectsignallingen
dc.subjectfacial developmenten
dc.subjectprotein dieten
dc.subjectCAGE-sequencingen
dc.subjectGWASen
dc.subjectmicroCTen
dc.titleThe level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signalingen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-188572en
sync.item.dbtypeVAVen
sync.item.insts2024.10.14 11:04:07en
sync.item.modts2024.09.11 15:32:05en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Pokročilé instrumentace a metody pro charakterizace materiálůcs
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