Guo Beibei, Qi Mengwei, Huang Shuai, Zhuo Run, Zhang Wenxue, Zhang Yufang, Xu Man, Liu Mei, Guan Tuchen, Liu Yan
Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Front Cell Dev Biol. 2021 Nov 8;9:768970. doi: 10.3389/fcell.2021.768970. eCollection 2021.
Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, and differentiation. In this study, we identified Cadherin-12 (CDH12), which encodes a type II classical cadherin, as a gene that promotes neurite outgrowth in an model of neurons with differentiated intrinsic growth ability. First, the effects of CDH12 on neurons were evaluated RNA interference, and the results indicated that the knockdown of CDH12 expression restrained the axon extension of E18 neurons. The transcriptome profile of neurons with or without siCDH12 treatment revealed a set of pathways positively correlated with the effect of CDH12 on neurite outgrowth. We further revealed that CDH12 affected Rac1/Cdc42 phosphorylation in a PKA-dependent manner after testing using H-89 and 8-Bromo-cAMP sodium salt. Moreover, we investigated the expression of CDH12 in the brain, spinal cord, and dorsal root ganglia (DRG) during development using immunofluorescence staining. After that, we explored the effects of CDH12 on neurite outgrowth . A zebrafish model of CDH12 knockdown was established using the NgAgo-gDNA system, and the vital role of CDH12 in peripheral neurogenesis was determined. In summary, our study is the first to report the effect of CDH12 on axonal extension and , and we provide a preliminary explanation for this mechanism.
钙黏蛋白在组织稳态中发挥着重要作用，因为它们在胚胎发生、组织形态发生和分化过程中负责细胞间黏附。在本研究中，我们鉴定出编码II型经典钙黏蛋白的钙黏蛋白-12（CDH12），它是在具有分化内在生长能力的神经元模型中促进神经突生长的基因。首先，通过RNA干扰评估了CDH12对神经元的影响，结果表明敲低CDH12表达会抑制E18神经元的轴突延伸。有无siCDH12处理的神经元转录组图谱揭示了一组与CDH12对神经突生长的影响呈正相关的通路。在使用H-89和8-溴-cAMP钠盐进行测试后，我们进一步发现CDH12以PKA依赖的方式影响Rac1/Cdc42磷酸化。此外，我们使用免疫荧光染色研究了发育过程中CDH12在脑、脊髓和背根神经节（DRG）中的表达。之后，我们探究了CDH12对神经突生长的影响。使用NgAgo-gDNA系统建立了CDH12敲低的斑马鱼模型，并确定了CDH在周围神经发生中的重要作用。总之，我们的研究首次报道了CDH12对轴突延伸的影响，并为此机制提供了初步解释。
