Mechanosensing is critical for axon growth in the developing brain.
Mechanosensing is critical for axon growth in the developing brain.
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DOI：
10.1038/nn.4394
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发表时间：
2016-12
影响因子：
25
通讯作者：
Franze K
中科院分区：
文献类型：
--
作者：
Koser DE;Thompson AJ;Foster SK;Dwivedy A;Pillai EK;Sheridan GK;Svoboda H;Viana M;Costa LD;Guck J;Holt CE;Franze K
在神经系统发育过程中，神经元沿着沿着明确的路径延伸轴突。目前对轴突寻路的理解主要基于化学信号。然而，生长中的神经元不仅在化学上，而且在机械上与环境相互作用。在这里，我们确定机械信号作为重要的调节轴突寻路。在体外，基板刚度决定非洲爪蟾视网膜神经节细胞（RGC）轴突的生长模式。在体内原子力显微镜显示惊人的刚度梯度模式在胚胎大脑。RGC轴突向组织较软的一侧生长，这在没有化学梯度的情况下在体外重现。为了测试机械信号对体内轴突生长的重要性，我们改变了大脑硬度，阻断了机械转导通路，并敲低了机械敏感离子通道Piezo1。所有的治疗导致异常轴突生长和寻路错误，这表明局部组织硬度机械敏感离子通道读出是至关重要的参与指导体内神经元的生长。
During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signalling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell (RGC) axons. In vivo atomic force microscopy revealed striking stiffness gradient patterns in the embryonic brain. RGC axons grew towards the tissue’s softer side, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically, and knocked down the mechanosensitive ion channel Piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness–read out by mechanosensitive ion channels–is critically involved in instructing neuronal growth in vivo.
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DOI：
10.4161/chan.21050
发表时间：
2012-07
期刊：
Channels (Austin, Tex.)
影响因子：
--
作者：
Gottlieb PA;Sachs F
通讯作者：
Sachs F
影响因子：
64.8
作者：
Coste, Bertrand;Xiao, Bailong;Santos, Jose S.;Syeda, Ruhma;Grandl, Joerg;Spencer, Kathryn S.;Kim, Sung Eun;Schmidt, Manuela;Mathur, Jayanti;Dubin, Adrienne E.;Montal, Mauricio;Patapoutian, Ardem
通讯作者：
Patapoutian, Ardem
影响因子：
4.6
作者：
Franze, Kristian
通讯作者：
Franze, Kristian
影响因子：
3.4
作者：
Isenberg, Brett C.;DiMilla, Paul A.;Wong, Joyce Y.
通讯作者：
Wong, Joyce Y.
影响因子：
2.4
作者：
Christ, Andreas F.;Franze, Kristian;Guck, Jochen
通讯作者：
Guck, Jochen