DCC mediated axon guidance of spinal interneurons is essential for normal locomotor central pattern generator function
DCC mediated axon guidance of spinal interneurons is essential for normal locomotor central pattern generator function
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DOI：
10.1016/j.ydbio.2012.03.017
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发表时间：
2012-06-15
影响因子：
2.7
通讯作者：
Kullander, Klas
中科院分区：
文献类型：
--
作者：
Bernhardt, Nadine Rabe;Memic, Fatima;Kullander, Klas
肢体有节奏的协调运动是通过局部脊髓神经元网络中有组织的信号传导来实现的。在发育过程中，这些回路的建立依赖于轴突对其目标的正确引导。先前的研究表明，众所周知的轴突引导分子netrin-1是配置有效运动中提供左右交替协调的电路所必需的。连接轴突对netrin-1反应的中线吸引已被证明涉及netrin-1受体DCC（在结直肠癌中缺失）。但是，发展协调会在建立方案协调组协调方面的作用尚未得到解决。我们发现，携带DCC零突变的小鼠在实际运动中表现出不协调的左右活动，并伴有源自互交祖细胞的神经元间亚群的丢失。因此，DCC在协调左右活动的脊髓神经回路的形成中起着至关重要的作用。结合先前发表的netrin-1缺陷小鼠的结果，本研究提供的数据表明，大多数起源于腹侧的V3中间神经元在中线上的同步活动中起作用。此外，它提供的证据表明，脊髓中的轴突交叉比之前提出的DCC-netrin-1相互作用模型更复杂地控制。(C) 2012爱思唯尔公司版权所有。
Coordinated limb rhythmic movements take place through organized signaling in local spinal cord neuronal networks. The establishment of these circuitries during development is dependent on the correct guidance of axons to their targets. It has previously been shown that the well-known axon guidance molecule netrin-1 is required for configuring the circuitry that provides left-right alternating coordination in fictive locomotion. The attraction of commissural axons to the midline in response to netrin-1 has been shown to involve the netrin-1 receptor DCC (deleted in Colorectal Cancer). However, the role of DCC for the establishment of CPG coordination has not yet been resolved. We show that mice carrying a null mutation of DCC displayed an uncoordinated left-right activity during fictive locomotion accompanied by a loss of interneuronal subpopulations originating from commissural progenitors. Thus, DCC plays a crucial role in the formation of spinal neuronal circuitry coordinating left-right activities. Together with the previously published results from netrin-1 deficient mice, the data presented in this study suggest a role for the most ventral originating V3 interneurons in synchronous activities over the midline. Further, it provides evidence that axon crossing in the spinal cord is more intricately controlled than in previously suggested models of DCC-netrin-1 interaction. (C) 2012 Elsevier Inc. All rights reserved.