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Transcriptional dysregulation in developing trigeminal sensory neurons in the LgDel mouse model of DiGeorge 22q11.2 deletion syndrome

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dc.contributor.authorMaynard, Thomas M.en
dc.contributor.authorHorvath, Aneliaen
dc.contributor.authorBernot, James P.en
dc.contributor.authorKarpinski, Beverly A.en
dc.contributor.authorTavares, Andre L. P.en
dc.contributor.authorShah, Ankitaen
dc.contributor.authorZheng, Qianqianen
dc.contributor.authorSpurr, Liamen
dc.contributor.authorOlender, Jacquelineen
dc.contributor.authorMoody, Sally A.en
dc.contributor.authorFraser, Claire M.en
dc.contributor.authorLaMantia, Anthony-Samuelen
dc.contributor.authorLee, Norman H.en
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2021-01-06T13:38:20Zen
dc.date.available2021-01-06T13:38:20Zen
dc.date.issued2020-03-15en
dc.description.abstractLgDel mice, which model the heterozygous deletion of genes at human chromosome 22q11.2 associated with DiGeorge/22q11.2 deletion syndrome (22q11DS), have cranial nerve and craniofacial dysfunction as well as disrupted suckling, feeding and swallowing, similar to key 22q11DS phenotypes. Divergent trigeminal nerve (CN V) differentiation and altered trigeminal ganglion (CNgV) cellular composition prefigure these disruptions in LgDel embryos. We therefore asked whether a distinct transcriptional state in a specific population of early differentiating LgDel cranial sensory neurons, those in CNgV, a major source of innervation for appropriate oropharyngeal function, underlies this departure from typical development. LgDel versus wild-type (WT) CNgV transcriptomes differ significantly at E10.5 just after the ganglion has coalesced. Some changes parallel altered proportions of cranial placode versus cranial neural crest-derived CNgV cells. Others are consistent with a shift in anterior-posterior patterning associated with divergent LgDel cranial nerve differentiation. The most robust quantitative distinction, however, is statistically verifiable increased variability of expression levels for most of the over 17 000 genes expressed in common in LgDel versus WT CNgV. Thus, quantitative expression changes of functionally relevant genes and increased stochastic variation across the entire CNgV transcriptome at the onset of CN V differentiation prefigure subsequent disruption of cranial nerve differentiation and oropharyngeal function in LgDel mice.en
dc.description.notesNational Institute of Child Health and Human Development (P01 HD083157).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]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1093/hmg/ddaa024en
dc.identifier.eissn1460-2083en
dc.identifier.issn0964-6906en
dc.identifier.issue6en
dc.identifier.pmid32047912en
dc.identifier.urihttp://hdl.handle.net/10919/101755en
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.titleTranscriptional dysregulation in developing trigeminal sensory neurons in the LgDel mouse model of DiGeorge 22q11.2 deletion syndromeen
dc.title.serialHuman Molecular Geneticsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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