Cdh1-APC controls axonal growth and patterning in the mammalian brain
Cdh1-APC controls axonal growth and patterning in the mammalian brain
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DOI：
10.1126/science.1093712
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发表时间：
2004-02-13
期刊：
影响因子：
56.9
通讯作者：
Bonni, A
中科院分区：
文献类型：
--
作者：
Konishi, Y;Stegm端ller, J;Bonni, A
后期促进复合物（APC）在有丝分裂后的神经元中高度表达，但其在神经系统中的功能此前并不清楚。我们报道，在原代神经元中抑制Cdh1 - APC可特异性地促进轴突生长。在小脑脑片覆盖试验以及在体内发育的大鼠小脑中对Cdh1进行敲低，揭示了颗粒神经元轴突的层特异性生长以及平行纤维模式形成方面的细胞自主性异常。还发现神经元中的Cdh1 RNA干扰可克服髓鞘对轴突生长的抑制作用。因此，Cdh1 - APC似乎在发育中的大脑中对轴突生长和模式形成起调节作用，这可能也限制了成年大脑中受损轴突的生长。
The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system was previously unknown. We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth. Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat cerebellum in vivo revealed cell-autonomous abnormalities in layer-specific growth of granule neuron axons and parallel fiber patterning. Cdh1 RNA interference in neurons was also found to override the inhibitory influence of myelin on axonal growth. Thus, Cdh1-APC appears to play a role in regulating axonal growth and patterning in the developing brain that may also limit the growth of injured axons in the adult brain.