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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Expression of liver X receptor β is essential for formation of superficial cortical layers and migration of later-born neurons
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Expression of liver X receptor β is essential for formation of superficial cortical layers and migration of later-born neurons

机译：肝脏X受体β的表达对于表皮层的形成和后代神经元的迁移至关重要

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摘要

Liver X receptor (LXR) β regulates cholesterol levels in the brain and is essential for maintenance of motor neurons in the spinal cord and dopaminergic neurons in the substantia nigra. Here, we have examined the expression pattern of LXRβ protein in the cerebral cortex and looked for defects in cortical development in LXRβ knockout (LXRβ~(-/-)) mice. LXRβ protein was widely expressed in the mouse brain at later embryonic stages, and the expression pattern in the cerebral cortex was developmentally regulated. In normal postnatal mice, LXRβ was localized mainly in the upper layers of the cerebral cortex. In LXRβ~(-/-) mice layers Ⅱ and Ⅲ were thinner with fewer neurons. Layer I was slightly thicker, whereas layers Ⅳ-Ⅵ were essentially normal. Consistent with this finding, Brn2 and NeuN expression were decreased in the upper layers in the LXRβ~(-/-) neonatal cortex. The number of S-phase progenitor cells in the cortex between embryonic day (E) 12.5 to E16.5, was similar in WT and LXRβ~(-/-) littermates but BrdU birth dating revealed that late-generated neurons labeled by BrdU injections administered at E14.5 or E16.5, and destined to cortical layers Ⅱ/Ⅲ, were disorganized and failed to migrate. The defect in migration appears to be caused by a reduction in the number of vertical processes emanating from the radial glia. These processes are the architectural guides for later-born migrating neurons. Taken together, these findings suggest that LXRβ expression in the cerebral cortex is involved in cortex lamination and is essential for the migration of late-generated neocortical neurons.
机译：肝脏X受体（LXR）β调节大脑中的胆固醇水平，对于维持脊髓中的运动神经元和黑质中的多巴胺能神经元至关重要。在这里，我们检查了LXRβ蛋白在大脑皮层中的表达模式，并寻找LXRβ基因敲除（LXRβ〜（-/-））小鼠的皮质发育缺陷。 LXRβ蛋白在后期胚胎阶段在小鼠大脑中广泛表达，并且大脑皮层中的表达模式受到发育调控。在正常的产后小鼠中，LXRβ主要位于大脑皮层的上层。在LXRβ〜（-/-）小鼠中，第Ⅱ和Ⅲ层较薄，神经元较少。 I层稍厚，而Ⅳ-Ⅵ层基本正常。与该发现一致的是，LXRβ〜（-/-）新生皮层的上层Brn2和NeuN表达降低。在胚胎天（E）12.5至E16.5之间，皮层中S期祖细胞的数量与野生型和LXRβ〜（-/-）同窝仔相似，但BrdU出生日期显示，用BrdU注射标记的晚期神经元在E14.5或E16.5处给药，并到达皮层Ⅱ/Ⅲ，它们杂乱无章，无法迁移。迁移的缺陷似乎是由于放射状神经胶质引起的垂直过程数量减少所致。这些过程是后来出生的迁移神经元的体系结构指南。综上所述，这些发现表明，大脑皮层中的LXRβ表达与皮质层积有关，并且对于后期生成的新皮层神经元的迁移至关重要。

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