Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system.
Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system.
复制标题
DOI：
10.1016/j.neuron.2008.06.028
复制
发表时间：
2008-08-28
期刊：
影响因子：
16.2
通讯作者：
Nave, Klaus Armin
中科院分区：
文献类型：
--
作者：
Brinkmann, Bastian G.;Agarwal, Amit;Sereda, Michael W.;Garratt, Alistair N.;Mueller, Thomas;Wende, Hagen;Stassart, Ruth M.;Nawaz, Schanila;Humml, Christian;Velanac, Viktorija;Radyushkin, Konstantin;Goebbels, Sandra;Fischer, Tobias M.;Franklin, Robin J.;Lai, Cary;Ehrenreich, Hannelore;Birchmeier, Carmen;Schwab, Markus H.;Nave, Klaus Armin
了解少突胶质细胞对髓鞘形成的控制对于治疗脱髓鞘疾病至关重要。Neuregulin-1（NRG 1）III型是一种EGF样生长因子，对PNS的髓鞘形成至关重要。因此，认为NRG 1/ErbB信号传导也调节CNS髓鞘形成，这一观点由体外研究和显性负性ErbB受体的过表达提出。为了直接验证这一假设，我们产生了一系列条件无效突变体，这些突变体从神经发育的不同阶段开始完全缺乏NRG 1。出乎意料的是，这些小鼠组装了正常数量的髓鞘。此外，缺乏少突胶质细胞ErbB 3和ErbB 4的双突变体在没有神经调节蛋白的任何刺激的情况下变得有髓鞘。相反，通过转基因过表达NRG 1 I型或NRG 1 III型实现显著的髓鞘形成过度。因此，NRG 1/ErbB信号是显着不同的雪旺细胞和少突胶质细胞已经发展了一个NRG/ErbB独立的髓鞘形成控制机制。
Understanding the control of myelin formation by oligodendrocytes is essential for treating demyelinating diseases. Neuregulin-1 (NRG1) type III, an EGF-like growth factor, is essential for myelination in the PNS. It is thus thought that NRG1/ErbB signaling also regulates CNS myelination, a view suggested by in vitro studies and the overexpression of dominant-negative ErbB receptors. To directly test this hypothesis, we generated a series of conditional null mutants that completely lack NRG1 beginning at different stages of neural development. Unexpectedly, these mice assemble normal amounts of myelin. In addition, double-mutants lacking oligodendroglial ErbB3 and ErbB4 become myelinated in the absence of any stimulation by neuregulins. In contrast, a significant hypermyelination is achieved by transgenic overexpression of NRG1 type I or NRG1 type III. Thus, NRG1/ErbB signaling is markedly different between Schwann cells and oligodendrocytes that have evolved a NRG/ErbB-independent mechanism of myelination control.
登录
查看更多内容
影响因子：
16.2
作者：
Canoll, PD;Musacchio, JM;Salzer, JL
通讯作者：
Salzer, JL
影响因子：
3.5
作者：
Canoll, PD;Kraemer, R;Salzer, JL
通讯作者：
Salzer, JL
影响因子：
16.2
作者：
Flames, N;Long, JE;Marín, O
通讯作者：
Marín, O
影响因子：
2.7
作者：
Golub, MS;Germann, SL;Lloyd, KCK
通讯作者：
Lloyd, KCK
影响因子：
5.3
作者：
Calaora, V;Rogister, B;Dubois-Dalcq, M
通讯作者：
Dubois-Dalcq, M