Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis.
Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis.
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DOI：
10.1371/journal.pgen.1006440
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发表时间：
2016-11
期刊：
影响因子：
4.5
通讯作者：
Granato M
中科院分区：
文献类型：
--
作者：
Bremer J;Granato M
在胚胎发生过程中，脊髓相对于邻近组织沿前后轴移位。胞体位于脊髓而轴突位于邻近组织的运动神经元如何补偿这种组织移位尚不清楚。利用斑马鱼的活细胞成像，我们发现当运动轴突离开脊髓并穿过相邻脊索细胞产生的细胞外基质时，这些细胞尾部移动了几个细胞直径。尽管有这种明显的变化，但单个运动神经元细胞体与其延伸的轴突保持一致。我们发现这种排列需要运动神经元内的肌球蛋白磷酸酶活性，而肌球蛋白磷酸酶亚基mypt1的突变增加了肌球蛋白磷酸化，导致运动神经元细胞体与其轴突之间的位移。因此，我们证明了脊髓运动神经元在轴突发生过程中微调它们的位置，我们确定肌球蛋白II调节网络是一个关键的调节剂。胚胎发育需要组织之间的紧密协调，因为它们经常以不同的速度生长。这种不同的生长速度会导致相邻组织之间的转移，对于跨越多个组织的单个细胞来说，这是一个特别的挑战，部分原因是这些细胞的机械张力预计会很高。在这里，我们研究运动神经元，其细胞体驻留在脊髓，而他们的轴突穿越邻近组织如何补偿组织移位。我们发现，在斑马鱼中，运动轴突延伸到相邻组织时，脊髓和相邻组织都以不同的速度生长，并相互移动位置。尽管有这种明显的变化，但单个运动神经元细胞体与其延伸的轴突保持一致。我们证明运动神经元中运动蛋白肌球蛋白II的调控网络是这种排列的关键，因为肌球蛋白磷酸酶亚基mypt1的突变增加了肌球蛋白磷酸化并导致运动神经元细胞体与其轴突之间的位移。从鱼类到人类，脊髓和邻近组织之间的运动都是保守的，因此，哺乳动物中很可能存在类似的机制，以确保正确的神经元排列，以补偿组织的移动。
During embryogenesis the spinal cord shifts position along the anterior-posterior axis relative to adjacent tissues. How motor neurons whose cell bodies are located in the spinal cord while their axons reside in adjacent tissues compensate for such tissue shift is not well understood. Using live cell imaging in zebrafish, we show that as motor axons exit from the spinal cord and extend through extracellular matrix produced by adjacent notochord cells, these cells shift several cell diameters caudally. Despite this pronounced shift, individual motoneuron cell bodies stay aligned with their extending axons. We find that this alignment requires myosin phosphatase activity within motoneurons, and that mutations in the myosin phosphatase subunit mypt1 increase myosin phosphorylation causing a displacement between motoneuron cell bodies and their axons. Thus, we demonstrate that spinal motoneurons fine-tune their position during axonogenesis and we identify the myosin II regulatory network as a key regulator. Embryonic development requires tight coordination between tissues as they frequently grow at different rates. Such differential growth rates can cause shifts between neighboring tissues, and are a particular challenge for individual cells that span multiple tissues, in part because mechanical tension on such cells is predicted to be high. Here we examine how motoneurons whose cell bodies reside in the spinal cord while their axons traverse adjacent tissues compensate for tissue shifts. We find that in zebrafish, motor axons extend into adjacent tissues at a time when both, spinal cord and adjacent tissues grow at different rates and shift positions against each other. Despite this pronounced shift, individual motoneuron cell bodies stay aligned with their extending axons. We demonstrate that the regulatory network of the molecular motor protein myosin II in motor neurons is key for this alignment as mutations in the myosin phosphatase subunit mypt1 increase myosin phosphorylation and cause a displacement between motoneuron cell bodies and their axons. Movements between spinal cord and adjacent tissues are conserved from fish to humans, and it is therefore likely that similar mechanisms exist in mammals to ensure correct neuronal alignment to compensate for tissue shifts.
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影响因子：
2.5
作者：
Barresi, Michael J. F.;Burton, Sean;Dipietrantonio, Kristina;Amsterdam, Adam;Hopkins, Nancy;Karlstrom, Rolf O.
通讯作者：
Karlstrom, Rolf O.
影响因子：
56.9
作者：
EISEN, JS
通讯作者：
EISEN, JS
影响因子：
4.8
作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
DOI：
10.1007/s13361-010-0051-2
发表时间：
2011-03
影响因子：
3.2
作者：
Geetha, Thangiah;Langlais, Paul;Luo, Moulun;Mapes, Rebekka;Lefort, Natalie;Chen, Shu-Chuan;Mandarino, Lawrence J.;Yi, Zhengping
通讯作者：
Yi, Zhengping