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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning
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Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning

机译：内源性大麻素信号控制锥体细胞的规格和远距离轴突模式

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摘要

Endocannabinoids (eCBs) have recently been identified as axon guidance cues shaping the connectivity of local GABAergic inter-neurons in the developing cerebrum. However, eCB functions during pyramidal cell specification and establishment of long-range axonal connections are unknown. Here, we show that eCB signaling is operational in subcortical proliferative zones from embryonic day 12 in the mouse telencephalon and controls the proliferation of pyramidal cell progenitors and radial migration of immature pyramidal cells. When layer patterning is accomplished, developing pyramidal cells rely on eCB signaling to initiate the elongation and fasciculation of their long-range axons. Accordingly, CB_1 cannabinoid receptor (CB_1R) null and pyramidal cell-specific conditional mutant (CB_1R~(f/f, NEX-Cre)) mice develop deficits in neuronal progenitor proliferation and axon fasciculation. Likewise, axonal pathfinding becomes impaired after in utero pharmacological blockade of CB_1Rs. Overall, eCBs are fundamental developmental cues controlling pyramidal cell development during corticogenesis.
机译：内源性大麻素（eCBs）最近已被确认为轴突引导线索，可塑造发育中的大脑中局部GABA能神经元的连通性。但是，在锥体细胞规范和长距离轴突连接建立过程中eCB的功能尚不清楚。在这里，我们显示eCB信号从小鼠端脑的胚胎第12天起在皮层下增生区中起作用，并控制锥体细胞祖细胞的增殖和未成熟锥体细胞的径向迁移。当完成层构图时，正在发育的锥体细胞依靠eCB信号来启动其长轴突的伸长和束缚。因此，CB_1大麻素受体（CB_1R）无效和锥体细胞特异性条件突变体（CB_1R〜（f / f，NEX-Cre））小鼠在神经元祖细胞增殖和轴突絮凝中出现缺陷。同样，在子宫内对CB_1Rs进行药理学阻断后，轴突寻路也受到损害。总体而言，eCBs是在皮质发生过程中控制锥体细胞发育的基本发育线索。

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