Motahari, ZahraMaynard, Thomas M.Popratiloff, AnastasMoody, Sally A.LaMantia, Anthony-Samuel2021-02-162021-02-162020-09-150964-6906http://hdl.handle.net/10919/102381We 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.application/pdfenCreative Commons Attribution-NonCommercial 4.0 InternationalArticle - Refereedhttps://doi.org/10.1093/hmg/ddaa1992918329012871460-2083