Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation.
Slit/Robo1 signaling regulates neural tube development by balancing neuroepithelial cell proliferation and differentiation.
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DOI：
10.1016/j.yexcr.2013.02.011
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发表时间：
2013-05
影响因子：
3.7
通讯作者：
Guang Wang;Yan Li;Xiao-yu Wang;Zhe Han;Manli Chuai;Li-jing Wang;K. H. Ho Lee;J. Geng;Xuesong Yang
中科院分区：
文献类型：
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作者：
Guang Wang;Yan Li;Xiao-yu Wang;Zhe Han;Manli Chuai;Li-jing Wang;K. H. Ho Lee;J. Geng;Xuesong Yang
神经管的形成是胚胎中枢神经系统（CNS）发育的形态标志。因此，神经管发育是神经形成过程中的关键步骤。 Slit/Robo 信号传导最初被认为是一种调节轴突生长锥伸长的化学排斥剂，但其在控制神经管发育中的作用目前尚不清楚。为了解决这个问题，我们研究了邓迪大学生命科学生物中心小鸡 neCollege of Life Sciences Biocentre、Dundee DD1 5EH、UKural tube 和过表达 Slit2 的转基因小鼠发育中的 Slit/Robo1 信号传导。我们通过将 R5 单克隆抗体注射到 HH10 神经管中来阻断 Robo1 受体，从而破坏 Slit/Robo1 信号传导。这抑制了腹侧身体弯曲的正常发育，导致脊髓卷曲成S形。接下来，鸡胚神经管一侧的 Slit/Robo1 信号传导受到卵内电穿孔的干扰。我们发现干扰 Slit/Robo1 信号后神经管的形态显着异常。此外，我们确定沉默 Robo1 会抑制细胞增殖，而过度表达 Robo1 会增强细胞增殖。我们还研究了改变 Slit/Robo1 表达对发育中神经管中 Sonic Hedgehog (Shh) 和 Pax7 表达的影响。我们证明，过度表达 Robo1 会下调腹侧神经管中的 Shh 表达，并导致 HNK-1+ 迁移神经嵴细胞 (NCC) 的产生减少。此外，Robo1 过表达增强了背神经管中 Pax7 的表达，并增加了 Slug+ 迁移前 NCC 的数量。相反，沉默Robo1表达导致Shh表达增强和更多HNK-1+迁移NCC，但观察到Pax7表达减少并且观察到更少的Slug+迁移前NCC。总之，我们提出 Slit/Robo1 信号传导通过在神经形成过程中紧密协调细胞增殖和分化来参与调节神经管发育。
Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1+migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug+pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1+migrating NCCs but reduced Pax7 expression and fewer Slug+pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly coordinating cell proliferation and differentiation during neurulation.