Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM promotes retinal axon midline crossing.

Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM promotes retinal axon midline crossing.
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DOI:
10.1016/j.neuron.2012.03.025
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发表时间:
2012-05-24
期刊:
影响因子:
16.2
通讯作者:
Mason C
Mason C
中科院分区:
医学1区
文献类型:
--
作者:
Kuwajima T;Yoshida Y;Takegahara N;Petros TJ;Kumanogoh A;Jessell TM;Sakurai T;Mason C

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在视交叉处,视网膜神经节细胞 (RGC) 向同侧或对侧投射,以建立双眼视觉的电路。同侧引导程序已被表征,但对侧引导程序尚不清楚。在这里,我们确定了对侧 RGC 投射的三重分子系统:Semaphorin 6D 和 Nr-CAM 在中线放射状胶质细胞上表达,Plexin-A1 在交叉神经元上表达,Plexin-A1 和 Nr-CAM 也在对侧 RGC 上表达。 Sema6D 对对侧 RGC 具有排斥作用,但 Sema6D 与 Nr-CAM 和 Plexin-A1 结合可将排斥作用转化为促进生长作用。 Nr-CAM 作为 Sema6D 的新型受体发挥作用。 Sema6D、Plexin-A1 和 Nr-CAM 都是视交叉处有效的 RGC 讨论所必需的。这些发现提出了一种新机制,交叉中线的 Sema6D、Nr-CAM 和 Plexin-A1 复合物通过改变 Sema6D 的信号并向 RGC 上的 Nr-CAM/Plexin-A1 受体发出信号以实现对侧 RGC 投射。
At the optic chiasm, retinal ganglion cells (RGCs) project ipsi- or contralaterally to establish the circuitry for binocular vision. Ipsilateral guidance programs have been characterized, but contralateral guidance programs are not well understood. Here we identify a tripartite molecular system for contralateral RGC projections: Semaphorin 6D and Nr-CAM are expressed on midline radial glia and Plexin-A1 on chiasm neurons, and Plexin-A1 and Nr-CAM are also expressed on contralateral RGCs. Sema6D is repulsive to contralateral RGCs, but Sema6D in combination with Nr-CAM and Plexin-A1 converts repulsion to growth-promotion. Nr-CAM functions as a novel receptor for Sema6D. Sema6D, Plexin-A1 and Nr-CAM are all required for efficient RGC decussation at the optic chiasm. These findings suggest a novel mechanism by which a complex of Sema6D, Nr-CAM, and Plexin-A1 at the chiasm midline alters the sign of Sema6D and signals Nr-CAM/Plexin-A1 receptors on RGCs to implement the contralateral RGC projection.
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