Aberrant early growth of individual trigeminal sensory and motor axons in a series of mouse genetic models of 22q11.2 deletion syndrome

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dc.contributor.authorMotahari, Zahraen
dc.contributor.authorMaynard, Thomas M.en
dc.contributor.authorPopratiloff, Anastasen
dc.contributor.authorMoody, Sally A.en
dc.contributor.authorLaMantia, Anthony-Samuelen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2021-02-16T13:49:46Zen
dc.date.available2021-02-16T13:49:46Zen
dc.date.issued2020-09-15en
dc.description.abstractWe identified divergent modes of initial axon growth that prefigure disrupted differentiation of the trigeminal nerve (CN V), a cranial nerve essential for suckling, feeding and swallowing (S/F/S), a key innate behavior compromised in multiple genetic developmental disorders including DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS). We combined rapid in vivo labeling of single CN V axons in LgDel(+/-) mouse embryos, a genomically accurate 22q11.2DS model, and 3D imaging to identify and quantify phenotypes that could not be resolved using existing methods. We assessed these phenotypes in three 22q11.2-related genotypes to determine whether individual CN V motor and sensory axons wander, branch and sprout aberrantly in register with altered anterior-posterior hindbrain patterning and gross morphological disruption of CN V seen in LgDel(+/-). In the additional 22q11.2-related genotypes: Tbx1(+/-), Ranbp1(+/-), Ranbp1(+/-) and LgDel(+/-):Raldh2(+/-); axon phenotypes are seen when hindbrain patterning and CN V gross morphology is altered, but not when it is normal or restored toward WT. This disordered growth of CN V sensory and motor axons, whose appropriate targeting is critical for optimal S/F/S, may be an early, critical determinant of imprecise innervation leading to inefficient oropharyngeal function associated with 22q11.2 deletion from birth onward.en
dc.description.notesNational Institute of Child Health and Human Development (P01 HD083157 to A.S.L.); NICHD IDDRC U54 (HD 090257 to G.W.); Georgetown University and Children's National Medical Center.en
dc.description.sponsorshipNational Institute of Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [P01 HD083157]; NICHD IDDRC U54 [HD 090257]; Georgetown University; Children's National Medical Centeren
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1093/hmg/ddaa199en
dc.identifier.eissn1460-2083en
dc.identifier.issn0964-6906en
dc.identifier.issue18en
dc.identifier.pmid32901287en
dc.identifier.urihttp://hdl.handle.net/10919/102381en
dc.identifier.volume29en
dc.language.isoenen
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.titleAberrant early growth of individual trigeminal sensory and motor axons in a series of mouse genetic models of 22q11.2 deletion syndromeen
dc.title.serialHuman Molecular Geneticsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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