Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice.
Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice.
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DOI：
10.3389/fnins.2020.570974
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发表时间：
2020
影响因子：
4.3
通讯作者：
Yamagishi S
中科院分区：
文献类型：
--
作者：
Ikegaya S;Iga Y;Mikawa S;Zhou L;Abe M;Sakimura K;Sato K;Yamagishi S
在成年小鼠脑中，神经发生主要发生在脑室-脑室下区（V-SVZ）和海马齿状回的颗粒下区。在V-SVZ中产生的神经母细胞响应于引导分子（例如netrin-1）通过吻侧迁移流（RMS）迁移到嗅球。我们以前表明，相关netrin-5（NTN 5）的表达在Mash 1阳性transit-amplifying细胞和doublecortin阳性神经母细胞的颗粒细胞层的嗅球，RMS，和成年小鼠大脑的颗粒下带。然而，NTN 5在成人神经发生中的确切作用尚未研究。在这项研究中，我们表明，在神经原性龛的增殖受损的NTN 5基因敲除小鼠。在V-SVZ中，NTN 5 KO小鼠中增殖（EdU标记）细胞的数量显著降低，而Ki 67阳性增殖细胞的数量不变，表明NTN 5 KO小鼠中细胞周期延长，细胞分裂减少。RMS和嗅球中EdU标记细胞的数量不变。相比之下，EdU标记的细胞在皮质，基底节/外侧隔核，胼胝体/前连合的数量增加，这主要是少突胶质细胞系细胞。最后，我们发现NTN 5 KO小鼠RMS中的链迁移是无序的。这些发现表明，NTN 5可能在促进V-SVZ龛的增殖、组织RMS中的适当链迁移和抑制脑中的少突细胞生成中发挥重要作用。
In the adult mouse brain, neurogenesis occurs mainly in the ventricular-subventricular zone (V-SVZ) and the subgranular zone of the hippocampal dentate gyrus. Neuroblasts generated in the V-SVZ migrate to the olfactory bulb via the rostral migratory stream (RMS) in response to guidance molecules, such as netrin-1. We previously showed that the related netrin-5 (NTN5) is expressed in Mash1-positive transit-amplifying cells and doublecortin-positive neuroblasts in the granule cell layer of the olfactory bulb, the RMS, and the subgranular zone of the adult mouse brain. However, the precise role of NTN5 in adult neurogenesis has not been investigated. In this study, we show that proliferation in the neurogenic niche is impaired in NTN5 knockout mice. The number of proliferating (EdU-labeled) cells in NTN5 KO mice was significantly lower in the V-SVZ, whereas the number of Ki67-positive proliferating cells was unchanged, suggesting a longer cell cycle and decreased cell division in NTN5 KO mice. The number of EdU-labeled cells in the RMS and olfactory bulb was unchanged. By contrast, the numbers of EdU-labeled cells in the cortex, basal ganglia/lateral septal nucleus, and corpus callosum/anterior commissure were increased, which largely represented oligodendrocyte lineage cells. Lastly, we found that chain migration in the RMS of NTN5 KO mice was disorganized. These findings suggest that NTN5 may play important roles in promoting proliferation in the V-SVZ niche, organizing proper chain migration in the RMS, and suppressing oligodendrogenesis in the brain.
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影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
影响因子：
64.8
作者：
Funato H;Miyoshi C;Fujiyama T;Kanda T;Sato M;Wang Z;Ma J;Nakane S;Tomita J;Ikkyu A;Kakizaki M;Hotta-Hirashima N;Kanno S;Komiya H;Asano F;Honda T;Kim SJ;Harano K;Muramoto H;Yonezawa T;Mizuno S;Miyazaki S;Connor L;Kumar V;Miura I;Suzuki T;Watanabe A;Abe M;Sugiyama F;Takahashi S;Sakimura K;Hayashi Y;Liu Q;Kume K;Wakana S;Takahashi JS;Yanagisawa M
通讯作者：
Yanagisawa M
影响因子：
5.3
作者：
Belvindrah, Richard;Hankel, Sabine;Muller, Ulrich
通讯作者：
Muller, Ulrich
DOI：
10.1006/bbrc.2000.2583
发表时间：
2000-05-10
影响因子：
3.1
作者：
Kappler, J;Franken, S;Koch, KW
通讯作者：
Koch, KW
影响因子：
3
作者：
Lallemand, Y;Luria, V;Lonai, P
通讯作者：
Lonai, P