Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning
Endocannabinoid signaling controls pyramidal cell specification and long-range axon patterning
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DOI：
10.1073/pnas.0803545105
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发表时间：
2008-06-24
影响因子：
11.1
通讯作者：
Harkany, Tibor
中科院分区：
文献类型：
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作者：
Mulder, Jan;Aguado, Tania;Harkany, Tibor
内源性大麻素（Endocannabinoids，eCB）最近被确定为轴突引导线索，其在发育中的大脑中塑造局部GABA能中间神经元的连接。然而，eCB功能在锥体细胞规范和建立远程轴突连接是未知的。在这里，我们表明，eCB信号是可操作的皮质下增殖区从胚胎第12天在小鼠端脑和控制锥体细胞祖细胞的增殖和径向迁移的未成熟锥体细胞。当完成层图案化时，发育中的锥体细胞依赖于eCB信号传导来启动其长程轴突的伸长和成束。因此，CB、大麻素受体（CB 1 R）无效和锥体细胞特异性条件突变体（CB 1 Rf/f，NEX-Cre）小鼠在神经元祖细胞增殖和轴突成束方面出现缺陷。同样，在子宫内阻断CB（1）受体后，轴突的寻路能力也会受损。总的来说，eCB是皮质生成过程中控制锥体细胞发育的基本发育线索。
Endocannabinoids (eCBs) have recently been identified as axon guidance cues shaping the connectivity of local GABAergic interneurons 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, cannabinoid receptor (CB1R) null and pyramidal cell-specific conditional mutant (CB1Rf/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(1)Rs. Overall, eCBs are fundamental developmental cues controlling pyramidal cell development during corticogenesis.