Contactin-1/F3 Regulates Neuronal Migration and Morphogenesis Through Modulating RhoA Activity
Contactin-1/F3 Regulates Neuronal Migration and Morphogenesis Through Modulating RhoA Activity
复制标题
DOI：
10.3389/fnmol.2018.00422
复制
发表时间：
2018-11-20
影响因子：
4.8
通讯作者：
Tsai, Jin-Wu
中科院分区：
文献类型：
--
作者：
Chen, Yi-An;Lu, I-Ling;Tsai, Jin-Wu
在新皮层发育过程中，新生神经元从胚脑室区（VZ）沿沿着放射状纤维向皮层板（CP）迁移，以填充大脑皮层。这种径向迁移需要神经元和径向纤维之间的粘附活动，然而，过去的研究只确定了有限数量的粘附分子参与这一过程。Contactin-1/F3（Cntn 1）是一种在发育中的神经系统中表达的细胞粘附分子，对于许多关键发育事件（包括神经细胞粘附、神经突生长、轴突导向和髓鞘形成）是必需的。然而，Cntn 1在皮质发育过程中神经元迁移的潜在作用尚未研究。我们利用子宫内电穿孔技术在神经干细胞中导入短发夹状RNA（short hairpin RNA，shRNA）来敲低（KD）Cntn 1。我们发现Cntn 1 KD导致神经元迁移延迟。阻滞细胞的主导突起形态异常，在脑深部观察到较多的多极细胞，提示突起形成失调。有趣的是，Cntn 1 KD也导致RhoA的上调，RhoA是神经元迁移的负调节因子。通过显性阴性RhoA（N19）的表达干扰RhoA部分地挽救了由CntnlKD引起的神经元迁移缺陷。我们的研究结果表明，Cntn 1是一种新的粘附蛋白，它是神经元迁移所必需的，并通过调节RhoA信号通路调节新生皮层神经元的突起形成。
During neocortical development, newborn neurons migrate along radial fibers from the germinal ventricular zone (VZ) toward the cortical plate (CP) to populate the cerebral cortex. This radial migration requires adhesion activities between neurons and radial fibers; however, past research has identified only a limited number of adhesion molecules involved in this process. Contactin-1/F3 (Cntn1), a cell adhesion molecule expressed in the developing nervous system is essential for many key developmental events including neural cell adhesion, neurite outgrowth, axon guidance and myelination. However, the potential role of Cntn1 in neuronal migration during cortical development has not been investigated. Here we used in utero electroporation to introduce short hairpin RNA (shRNA) to knock down (KD) Cntn1 in neural stem cells in vivo. We found that Cntn1 KD led to a delay in neuronal migration. The arrested cells presented abnormal morphology in their leading process and more multipolar cells were observed in the deep layers of the brain, suggestive of dysregulation in process formation. Intriguingly, Cntn1 KD also resulted in upregulation of RhoA, a negative regulator for neuronal migration. Interference of RhoA by expression of the dominant - negative RhoA(N19) partially rescued the neuronal migration defects caused by Cntn1 KD. Our results showed that Cntn1 is a novel adhesion protein that is essential for neuronal migration and regulates process formation of newborn cortical neurons through modulating RhoA signaling pathway.