Axonal branching in lateral olfactory tract is promoted by Nogo signaling.

Axonal branching in lateral olfactory tract is promoted by Nogo signaling.
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DOI:
10.1038/srep39586
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发表时间:
2016-12-21
期刊:
影响因子:
4.6
通讯作者:
Takei K
Takei K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Iketani M;Yokoyama T;Kurihara Y;Strittmatter SM;Goshima Y;Kawahara N;Takei K

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二尖瓣细胞是嗅球(OB)的主要投射神经元,形成称为外侧嗅束(LOT)的轴突束。轴突束形成后,侧支从LOT的初级轴突上发出。最近,我们确定LOT引导物质(LOTUS)作为内源性Nogo受体-1(NgR 1)拮抗剂,并证明LOTUS有助于LOT轴突束的形成。免疫印迹显示,在轴突侧支形成过程中,OB中Nogo-A的表达水平发育性增加。接下来,我们发现,轴突侧支在LOTUS敲除(KO)小鼠培养的OB神经元中增加,而在NgR 1-KO小鼠培养的OB神经元中减少。在培养的OB神经元中敲除Nogo-A减少了轴突侧支的数量,表明内源性Nogo-A诱导轴突分支。最后,LOTUS-KO小鼠的LOT侧支增加,而NgR 1-KO小鼠的LOT侧支减少。此外,在LOTUS-KO小鼠中观察到的轴突分支的异常增加在LOTUS-和NgR 1-KO小鼠的双突变体中得到挽救。这些发现表明Nogo-A和NgR 1的相互作用可能有助于LOT发育中的轴突分支。
Mitral cells are major projection neurons of the olfactory bulb (OB) that form an axonal bundle known as the lateral olfactory tract (LOT). After axonal bundle formation, collateral branches sprout from primary axons of the LOT. Recently, we identified LOT usher substance (LOTUS) as an endogenous Nogo receptor-1 (NgR1) antagonist and demonstrated that LOTUS contributes to the formation of the LOT axonal bundle. Immunoblots revealed that the expression level of Nogo-A in the OB developmentally increased during axonal collateral formation. Next, we found that the axonal collateral branches were increased in cultured OB neurons from LOTUS-knockout (KO) mice, whereas they were decreased in cultured OB neurons from NgR1-KO mice. Knockdown of Nogo-A in cultured OB neurons reduced the number of axonal collateral branches, suggesting that endogenous Nogo-A induces axonal branching. Finally, the collateral branches of the LOT were increased in LOTUS-KO mice, whereas those in NgR1-KO mice were decreased. Moreover, the abnormal increase of axonal branching observed in LOTUS-KO mice was rescued in the double mutant of LOTUS- and NgR1-KO mice. These findings suggest that Nogo-A and NgR1 interactions may contribute to axonal branching in LOT development.
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