Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points.

Semaphorin-6A controls guidance of corticospinal tract axons at multiple choice points.
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DOI:
10.1186/1749-8104-3-34
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发表时间:
2008-12-08
期刊:
影响因子:
3.6
通讯作者:
Mitchell KJ
Mitchell KJ
中科院分区:
生物学3区
文献类型:
--
作者:
Rünker AE;Little GE;Suto F;Fujisawa H;Mitchell KJ

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皮质脊髓束(CST)轴突从皮质到脊髓的轨迹涉及一系列选择点,每个选择点都由多个引导分子控制。为了评估跨膜脑信号蛋白及其丛蛋白受体参与CST轴突的指导,我们研究了脑信号蛋白-6A(Sema 6A)、丛蛋白-A2(PlxnA 2)和丛蛋白-A4(PlxnA 4)的突变体中的这条道。我们描述了缺陷的CST指导Sema 6A突变体在选择点在中后脑边界(MHB)和导航通过脑桥,显着影响有多少轴突到达后脑和脊髓,并导致发育不全的CST。我们还观察到缺陷的指导,在后脑内的比例的轴突aberrantly采取腹外侧的位置,并未能交叉。后脑中的这种功能似乎是由已知的Sema 6A受体PlxnA 4介导的,该受体由CST轴突表达。然而,在MHB的指导,似乎独立于这一点和其他已知的受体,PlxnA 2,而可能取决于Sema 6A表达CST轴突本身在胚胎阶段。这些数据确定Sema 6A作为CST轴突在多个选择点的指导的主要贡献者。他们强调了主动控制的指导在MHB,也牵连下橄榄作为一个重要的结构,在指导的CST轴突在后脑。他们还表明,少突胶质细胞强烈表达的Sema 6A可能会影响成年人的CST再生。
The trajectory of corticospinal tract (CST) axons from cortex to spinal cord involves a succession of choice points, each of which is controlled by multiple guidance molecules. To assess the involvement of transmembrane semaphorins and their plexin receptors in the guidance of CST axons, we have examined this tract in mutants of Semaphorin-6A (Sema6A), Plexin-A2 (PlxnA2) and Plexin-A4 (PlxnA4). We describe defects in CST guidance in Sema6A mutants at choice points at the mid-hindbrain boundary (MHB) and in navigation through the pons that dramatically affect how many axons arrive to the hindbrain and spinal cord and result in hypoplasia of the CST. We also observe defects in guidance within the hindbrain where a proportion of axons aberrantly adopt a ventrolateral position and fail to decussate. This function in the hindbrain seems to be mediated by the known Sema6A receptor PlxnA4, which is expressed by CST axons. Guidance at the MHB, however, appears independent of this and of the other known receptor, PlxnA2, and may depend instead on Sema6A expression on CST axons themselves at embryonic stages. These data identify Sema6A as a major contributor to the guidance of CST axons at multiple choice points. They highlight the active control of guidance at the MHB and also implicate the inferior olive as an important structure in the guidance of CST axons within the hindbrain. They also suggest that Sema6A, which is strongly expressed by oligodendrocytes, may affect CST regeneration in adults.
DOI: 10.1038/nn976
发表时间: 2002-12-01
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