Mirra Serena, Ulloa Fausto, Gutierrez-Vallejo Irene, Martì Elisa, Soriano Eduardo
Department of Cell Biology, Faculty of Biology, University of BarcelonaBarcelona, Spain; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos IIIMadrid, Spain.
Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, ParcCientífic de Barcelona Barcelona, Spain.
Front Cell Neurosci. 2016 Mar 3;10:47. doi: 10.3389/fncel.2016.00047. eCollection 2016.
The eutherian X-chromosome specific family of Armcx genes has been described as originating by retrotransposition from Armc10/SVH, a single Arm-containing somatic gene. Armcx3 and Armc10/SVH are characterized by high expression in the central nervous system and they play an important role in the regulation of mitochondrial distribution and transport in neurons. In addition, Armcx/Arm10 genes have several Armadillo repeats in their sequence. In this study we address the potential role of this gene family in neural development by using the chick neural tube as a model. We show that Armc10/SVH is expressed in the chicken spinal cord, and knocking-down Armc10/SVH by sh-RNAi electroporation in spinal cord reduces proliferation of neural precursor cells (NPCs). Moreover, we analyzed the effects of murine Armcx3 and Armc10 overexpression, showing that both proteins regulate progenitor proliferation, while Armcx3 overexpression also specifically controls neural maturation. We show that the phenotypes found following Armcx3 overexpression require its mitochondrial localization, suggesting a novel link between mitochondrial dynamics and regulation of neural development. Furthermore, we found that both Armcx3 and Armc10 may act as inhibitors of Wnt-β-catenin signaling. Our results highlight both common and differential functions of Armcx/Armc10 genes in neural development in the spinal cord.
有袋类X染色体特异性Armcx基因家族被认为起源于Armc10/SVH的逆转座,Armc10/SVH是一个含单个犰狳重复序列的体细胞基因。Armcx3和Armc10/SVH的特征是在中枢神经系统中高表达,并且它们在神经元线粒体分布和运输的调节中发挥重要作用。此外,Armcx/Arm10基因在其序列中有几个犰狳重复序列。在本研究中,我们以鸡神经管为模型探讨了该基因家族在神经发育中的潜在作用。我们发现Armc10/SVH在鸡脊髓中表达,通过脊髓内sh-RNAi电穿孔敲低Armc10/SVH可减少神经前体细胞(NPC)的增殖。此外,我们分析了小鼠Armcx3和Armc10过表达的影响,结果表明这两种蛋白均调节祖细胞增殖,而Armcx3过表达还特异性地控制神经成熟。我们发现Armcx3过表达后的表型依赖于其线粒体定位,提示线粒体动力学与神经发育调节之间存在新的联系。此外,我们发现Armcx3和Armc10均可作为Wnt-β-连环蛋白信号通路的抑制剂。我们的结果突出了Armcx/Armc10基因在脊髓神经发育中的共同和不同功能。