The Mechanism of Rap1 Regulates N-cadherin to Control Neuronal Migration
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Rap1 and N-cadherin regulate glia-independent translocation of cortical neurons. It remains unclear how Rap1 regulates N-cadherin-mediated neuronal migration. Here, we overexpressed Rap1gap in mouse brains (embryonic day 16) to inactivate Rap1, and observed that neurons did not migrate to the outer layer. We confirmed that Rap1 was involved in the regulation of late neurons in vivo. Rap1gap overexpression and Rap1 suppression in CHO cells decreased the expression of cytoskeletal proteins such as tubulin. Changes in the expression of cell morphology regulators, such as N-cadherin and β-catenin, were also observed. Inhibition of N-cadherin in mouse brains prevented neuronal migration to the outer layer. The morphology of CHO cells was changed after overexpression of Rap1gap. We propose that Rap1 regulates the expression of N-cadherin during embryonic development, which affects β-catenin expression. Beta-catenin in turn regulates cytoskeletal protein expression, ultimately affecting neuronal morphology and migration.
KeywordsRap1 N-cadherin In utero electroporation Mouse Neuron migration
Conceived and designed the experiments: Juntang Lin and Ciqing Yang. Performed the experiments: Ciqing Yang, Xiaoying Li, Bichao Zhang, Sulei Fu, Shuanqing Li, Jianing Shen, Lihong Guan, and Liang Qiao. Analyzed the data: Ciqing Yang. Wrote the paper: Ciqing Yang.
This work was supported by a grant from Henan Province Natural Science Foundation (162300410214, 14B310007), the Henan Province University youth researcher support program project (2015GGJS-133), the National Science Foundation of China (No 81771226, 81600987), the support project for the Disciplinary group of Psychology and Neuroscience, Xinxiang Medical University (2016PN-KFKT-03, 20172DCG-03), the Science and Technology Innovation Talents Support Program of Henan Universities and Xinxiang City (14HASTIT032, CXRC16003), Xinxiang major science and technology projects (ZD17008), the PhD Research Startup Foundation (505090) of Xinxiang Medical University, and Innovation of College Students Project (SKYLS005, 201710472011).
Compliance with Ethical Standards
Experiments were approved by the Animal Care Committee of Xinxiang Medical University (No. 030032). All animal protocols were conducted under the guidelines of The Ministry of Science and Technology of the People’s Republic of China [(2006)398].
The authors declare that they have no conflicts of interest.
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