Hayano Yasufumi, Sasaki Kensuke, Ohmura Nami, Takemoto Makoto, Maeda Yurie, Yamashita Toshihide, Hata Yoshio, Kitada Kazuhiro, Yamamoto Nobuhiko
Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan; Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan; and.
Laboratory of Cellular and Molecular Neurobiology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan;
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15226-31. doi: 10.1073/pnas.1402095111. Epub 2014 Oct 6.
Axon branching is remodeled by sensory-evoked and spontaneous neuronal activity. However, the underlying molecular mechanism is largely unknown. Here, we demonstrate that the netrin family member netrin-4 (NTN4) contributes to activity-dependent thalamocortical (TC) axon branching. In the postnatal developmental stages of rodents, ntn4 expression was abundant in and around the TC recipient layers of sensory cortices. Neuronal activity dramatically altered the ntn4 expression level in the cortex in vitro and in vivo. TC axon branching was promoted by exogenous NTN4 and suppressed by depletion of the endogenous protein. Moreover, unc-5 homolog B (Unc5B), which strongly bound to NTN4, was expressed in the sensory thalamus, and knockdown of Unc5B in thalamic cells markedly reduced TC axon branching. These results suggest that NTN4 acts as a positive regulator for TC axon branching through activity-dependent expression.
轴突分支通过感觉诱发和自发的神经元活动进行重塑。然而，其潜在的分子机制在很大程度上尚不清楚。在这里，我们证明了网蛋白家族成员网蛋白-4（NTN4）有助于依赖活动的丘脑皮质（TC）轴突分支。在啮齿动物出生后的发育阶段，ntn4在感觉皮层的TC接受层及其周围大量表达。神经元活动在体外和体内显著改变了皮层中ntn4的表达水平。外源性NTN4促进TC轴突分支，而内源性蛋白的缺失则抑制TC轴突分支。此外，与NTN4强烈结合的unc-5同源物B（Unc5B）在感觉丘脑中表达，丘脑细胞中Unc5B的敲低显著减少了TC轴突分支。这些结果表明，NTN4通过依赖活动的表达作为TC轴突分支的正向调节因子。
