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通过散乱蛋白、Rac和JNK的Wnt信号传导调节树突发育。

Wnt signaling through Dishevelled, Rac and JNK regulates dendritic development.

作者信息

Rosso Silvana B, Sussman Daniel, Wynshaw-Boris Anthony, Salinas Patricia C

机构信息

Department of Anatomy and Developmental Biology, Rockefeller Building, University College London, University Street, London WC1E 6BT, UK.

出版信息

Nat Neurosci. 2005 Jan;8(1):34-42. doi: 10.1038/nn1374. Epub 2004 Dec 19.

Abstract

Dendritic arborization is required for proper neuronal connectivity. Rho GTPases have been implicated in the regulation of dendrite development. However, the signaling pathways that impinge on these molecular switches remain poorly understood. Here we show that Wnt7b, which is expressed in the mouse hippocampus, increases dendritic branching in cultured hippocampal neurons. This effect is mimicked by the expression of Dishevelled (Dvl) and is blocked by Sfrp1, a secreted Wnt antagonist. Consistent with these findings, hippocampal neurons from mice lacking Dvl1 show reduced dendritic arborization. Activation of the canonical Wnt-Gsk3beta pathway does not affect dendritic development. In contrast, Wnt7b and Dvl activate Rac and JNK in hippocampal neurons. Dominant-negative Rac, dominant-negative JNK or inhibition of JNK blocks Dvl-mediated dendritic growth. These findings demonstrate a new function for the non-canonical Wnt pathway in dendrite development and identify Dvl as a regulator of Rho GTPases and JNK during dendritic morphogenesis.

摘要

树突分支对于正常的神经元连接至关重要。Rho GTP酶已被证明参与树突发育的调控。然而,影响这些分子开关的信号通路仍知之甚少。在此我们表明,在小鼠海马体中表达的Wnt7b可增加培养的海马神经元的树突分支。这种效应可被Dishevelled(Dvl)的表达模拟,并被分泌型Wnt拮抗剂Sfrp1阻断。与这些发现一致,缺乏Dvl1的小鼠的海马神经元显示出树突分支减少。经典Wnt-Gsk3β信号通路的激活不影响树突发育。相反,Wnt7b和Dvl可激活海马神经元中的Rac和JNK。显性负性Rac、显性负性JNK或JNK的抑制可阻断Dvl介导的树突生长。这些发现证明了非经典Wnt信号通路在树突发育中的新功能,并确定Dvl是树突形态发生过程中Rho GTP酶和JNK的调节因子。

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