Function of Armcx3 and Armc10/svh genes in the regulation of progenitor proliferation and neural differentiation in the chicken spinal cord

Abstract

The eutherian X-chromosome specific family of Armcx genes has been described asoriginating by retrotransposition from Armc10/SVH, a single Arm-containing somaticgene. Armcx3 and Armc10/SVH are characterized by high expression in the centralnervous system and they play an important role in the regulation of mitochondrialdistribution and transport in neurons. In addition, Armcx/Arm10 genes have severalArmadillo repeats in their sequence. In this study we address the potential role of thisgene family in neural development by using the chick neural tube as a model. Weshow that Armc10/SVH is expressed in the chicken spinal cord, and knocking-downArmc10/SVH by sh-RNAi electroporation in spinal cord reduces proliferation of neuralprecursor cells (NPCs). Moreover, we analyzed the effects of murine Armcx3 andArmc10 overexpression, showing that both proteins regulate progenitor proliferation,while Armcx3 overexpression also specifically controls neural maturation. We showthat the phenotypes found following Armcx3 overexpression require its mitochondriallocalization, suggesting a novel link between mitochondrial dynamics and regulation ofneural development. Furthermore, we found that both Armcx3 and Armc10 may act asinhibitors of Wnt-β-catenin signaling. Our results highlight both common and differentialfunctions of Armcx/Armc10 genes in neural development in the spinal cord.