Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance
Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance
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DOI：
10.1016/s0896-6273(00)00033-7
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发表时间：
2000-08-01
期刊：
影响因子：
16.2
通讯作者：
Rougon, G
中科院分区：
文献类型：
--
作者：
Castellani, V;Chédotal, A;Rougon, G
在人类中，皮质脊髓束的缺陷归因于编码L1 CAM基因的突变，这种表型在L1缺陷小鼠中也能复制。通过共培养实验，我们报道了从脊髓腹侧分泌的Sema3A排斥野生型小鼠的皮质轴突，而不排斥l1缺陷小鼠。L1和neuropilin-1 （NP-1）形成稳定的复合物，它们的胞外结构域可以直接结合。因此，L1是Sema3A受体复合物的一个组成部分，L1突变可能会破坏生长锥中的Sema3A信号传导，导致引导错误。添加可溶性L1Fc嵌合分子不能恢复l1缺陷轴突的Sema3A响应性；相反，它将野生型轴突的排斥转化为吸引，进一步支持L1在生长锥内Sema3A转导通路中的功能。
In humans, defects of the corticospinal tract have been attributed to mutations in the gene encoding L1 CAM, a phenotype that is reproduced in L1-deficient mice. Using coculture assays, we report that Sema3A secreted from the ventral spinal cord repels cortical axons from wild-type but not from L1-deficient mice. L1 and neuropilin-1 (NP-1) form a stable complex, and their extracellular domains can directly associate. Thus, L1 is a component of the Sema3A receptor complex, and L1 mutations may disrupt Sema3A signaling in the growth cone, leading to guidance errors. Addition of soluble L1Fc chimeric molecules does not restore Sema3A responsiveness of L1-deficient axons; instead, it converts the repulsion of wild-type axons into an attraction, further supporting a function for L1 in the Sema3A transducing pathways within the growth cone.