Wnt3a Ectopic Expression Interferes Axonal Projection and Motor Neuron Positioning During the Chicken Spinal Cord Development
Wnt3a Ectopic Expression Interferes Axonal Projection and Motor Neuron Positioning During the Chicken Spinal Cord Development
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Wnt3a 异位表达干扰鸡脊髓发育过程中的轴突投射和运动神经元定位
DOI：
10.1007/s12031-018-1060-z
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发表时间：
2018
影响因子：
3.1
通讯作者：
Lin Juntang
中科院分区：
文献类型：
--
作者：
Li Qiuling;Yang Ciqing;Zhang Bichao;Guo Zhikun;Lin Juntang
脊髓背腹轴的形成主要由背侧信号如Wnts（其是无翅+ MMTV整合体，Int家族的成员）控制，除了腹侧信号如音刺猬（Shh）。Wnt 3a是Wnt家族成员之一，参与多种细胞功能，包括自我更新、增殖、分化和运动。本研究旨在探讨Wnt 3a对鸡脊髓图案形成的调控机制。在这项研究中，Wnt 3a异位表达的发育鸡胚胎的脊髓通过卵内电穿孔。免疫荧光染色结果显示，Wnt 3a异位表达导致连合轴突投射异常，神经纤维形成中断。值得注意的是，Wnt 3a过表达后，心室区神经元，尤其是运动神经元，无法侧向迁移，导致运动柱畸形。此外，我们发现，神经元不能突出轴突后，过度表达Wnt 3a在脊髓。Wnt 3a过表达抑制了培养的SH-SY 5 Y细胞中突起的生长。总之，我们提出Wnt 3a调节神经元形态，随后在脊髓发育过程中破坏轴突投射和运动神经元定位。
The formation of dorsal-ventral axis of the spinal cord is controlled largely by dorsal signals such as Wnts (which are members of the wingless + MMTV integrants, Int family), besides ventral signals such as sonic hedgehog (Shh). Wnt3a, one of the Wnt family members, is involved in multiple cellular functions, including self-renewal, proliferation, differentiation, and motility. Here, we aim to study the mechanism of the regulation of chicken spinal cord patterning by Wnt3a. In this study, Wnt3a was ectopically expressed in the spinal cord of developing chicken embryos by in ovo electroporation. The results of immunofluorescent staining revealed that Wnt3a ectopic expression caused the abnormality of commissural axonal projection and the formation of nerve fibers was interrupted. It is worth noting that neurons in the ventricular zone, especially motor neurons, could not migrate laterally after the Wnt3a overexpression, which led to the malformation of motor column. In addition, we found that neurons could not protrude axons outwardly after overexpression of Wnt3a in the spinal cord. It was also found that Wnt3a overexpression inhibited the outgrowth of processes in culturing SH-SY5Y cells. In conclusion, we proposed that Wnt3a regulates neuronal morphology, which subsequently disrupts axonal projection and motor neuron positioning during spinal cord development.