Local retinoic acid signaling directs emergence of the extraocular muscle functional unit

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dc.contributor.authorComai, Glendacs
dc.contributor.authorTesařová, Markétacs
dc.contributor.authorDupé, Valériecs
dc.contributor.authorRhinn, Murielcs
dc.contributor.authorVallecillo-García, Pedrocs
dc.contributor.authorda Silva, Fabiocs
dc.contributor.authorFeret, Bettycs
dc.contributor.authorExelby, Katherinecs
dc.contributor.authorDolle, Pascalcs
dc.contributor.authorCarlsson, Leifcs
dc.contributor.authorPryce, Briancs
dc.contributor.authorSpitz, Francoiscs
dc.contributor.authorStricker, Sigmarcs
dc.contributor.authorZikmund, Tomášcs
dc.contributor.authorKaiser, Jozefcs
dc.contributor.authorBriscoe, Jamescs
dc.contributor.authorSchedl, Andreascs
dc.contributor.authorGhyselinck, Norbertcs
dc.contributor.authorSchweitzer, Ronencs
dc.contributor.authorTajbakhsh, Shahragimcs
dc.coverage.issue11cs
dc.coverage.volume18cs
dc.date.accessioned2020-12-08T11:56:22Z
dc.date.available2020-12-08T11:56:22Z
dc.date.issued2020-11-17cs
dc.description.abstractCoordinated development of muscles, tendons, and their attachment sites ensures emergence of functional musculoskeletal units that are adapted to diverse anatomical demands among different species. How these different tissues are patterned and functionally assembled during embryogenesis is poorly understood. Here, we investigated the morphogenesis of extraocular muscles (EOMs), an evolutionary conserved cranial muscle group that is crucial for the coordinated movement of the eyeballs and for visual acuity. By means of lineage analysis, we redefined the cellular origins of periocular connective tissues interacting with the EOMs, which do not arise exclusively from neural crest mesenchyme as previously thought. Using 3D imaging approaches, we established an integrative blueprint for the EOM functional unit. By doing so, we identified a developmental time window in which individual EOMs emerge from a unique muscle anlage and establish insertions in the sclera, which sets these muscles apart from classical muscle-to-bone type of insertions. Further, we demonstrate that the eyeballs are a source of diffusible all-trans retinoic acid (ATRA) that allow their targeting by the EOMs in a temporal and dose-dependent manner. Using genetically modified mice and inhibitor treatments, we find that endogenous local variations in the concentration of retinoids contribute to the establishment of tendon condensations and attachment sites that precede the initiation of muscle patterning. Collectively, our results highlight how global and site-specific programs are deployed for the assembly of muscle functional units with precise definition of muscle shapes and topographical wiring of their tendon attachments.en
dc.formattextcs
dc.format.extent1-33cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationPLOS BIOLOGY. 2020, vol. 18, issue 11, p. 1-33.en
dc.identifier.doi10.1371/journal.pbio.3000902cs
dc.identifier.issn1544-9173cs
dc.identifier.other166299cs
dc.identifier.urihttp://hdl.handle.net/11012/195766
dc.language.isoencs
dc.publisherPLOScs
dc.relation.ispartofPLOS BIOLOGYcs
dc.relation.urihttps://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000902cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1544-9173/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjecteyeen
dc.subjectextraocular musclesen
dc.subjectEOMen
dc.subjectembryogenesisen
dc.subjectdevelopmenten
dc.titleLocal retinoic acid signaling directs emergence of the extraocular muscle functional uniten
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-166299en
sync.item.dbtypeVAVen
sync.item.insts2021.01.07 16:58:45en
sync.item.modts2021.01.07 16:18:14en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Charakterizace materiálů a pokročilé povlaky 1-06cs
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