We 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 3-dimensional 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.

中文翻译：

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22q11.2 缺失综合征的一系列小鼠遗传模型中个体三叉神经感觉和运动轴突的异常早期生长。

我们确定了初始轴突生长的不同模式，这预示着破坏了三叉神经 (CN V) 的分化，这是一种对哺乳、喂养和吞咽 (S/F/S) 至关重要的颅神经，这是一种在多种遗传发育障碍中受损的关键先天行为，包括DiGeorge/22q11.2 缺失综合征 (22q11.2 DS)。我们结合了LgDel中单个 CN V 轴突的快速体内标记^+/-小鼠胚胎、基因组上准确的 22q11.2DS 模型和 3 维成像，以识别和量化使用现有方法无法解决的表型。我们评估了三种 22q11.2 相关基因型中的这些表型，以确定个体 CN V 运动和感觉轴突是否漂移、分支和发芽异常，与LgDel中所见的 CN V 前后脑模式改变和总体形态破坏相一致^+/- . 在额外的 22q11.2 相关基因型中：Tbx1 ^+/-、Ranbp1 ^-/-、Ranbp1 ^+/-和LgDel ^+/-：Raldh2 ^+/-; 当后脑模式和 CN V 大体形态发生改变时，可以看到轴突表型，但当它正常或恢复到 WT 时则不会。CN V 感觉轴突和运动轴突的这种无序生长，其适当的靶向对于最佳 S/F/S 至关重要，可能是导致与出生后 22q11.2 缺失相关的口咽功能效率低下的不精确神经支配的早期关键决定因素。