Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are short with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutants Ift122 and Ttc21b and embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.

中文翻译：

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声波刺猬信号在颅神经管闭合过程中指导模式化的细胞重塑

神经管闭合缺损是婴儿死亡的主要原因，其中运动占近三分之一。然而，对颅神经管闭合的机制尚不十分了解。在这里，我们显示此过程涉及由声波刺猬（Shh）信号控制的整个组织的根尖收缩。小鼠中脑神经上皮细胞的中线细胞较短，顶端表面较大，而侧细胞较高，并受到同步的根尖收缩，从而驱动神经折叠抬高。缺少Shh效应子Gli2的胚胎无法产生适当的中线细胞结构，而具有扩展Shh信号的胚胎，包括IFT-A复合突变体Ift122和Ttc21b表达活化的，平滑的，在顶部细胞中显示出顶端收缩缺陷的胚胎。外侧而不是中线细胞重塑的破坏会导致运动障碍。这些结果揭示了由Shh信号控制的模式性根尖收缩的形态发生程序，该信号在发育中的哺乳动物大脑中产生结构变化。