Abstract
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.
Highlights
In early neural development, the neural tube is formed by self-expanding neural precursor cells (NPCs); as neurogenesis proceeds, NPCs located in the ventricular zone progressively exit cell cycle and subsequently give rise to post-mitotic cells accumulating in the mantle zone
In the developing spinal cord, neural progenitors reside in the ventricular zone (VZ)
In mammals several members of the family are described (LópezDoménech et al, 2012), the only Armcx/Armc10 member found in chick is the Armc10 gene, producing two isoforms, FIGURE 7 | Endogenous Armc10 is expressed in chicken spinal cord. (A) Structure and domains of the two different isoforms of chicken Armc10 protein predicted by in silico analysis
Summary
The neural tube is formed by self-expanding neural precursor cells (NPCs); as neurogenesis proceeds, NPCs located in the ventricular zone progressively exit cell cycle and subsequently give rise to post-mitotic cells accumulating in the mantle zone. The dorsal-ventral gradient of Wnt/β-catenin signaling plays an essential role in maintaining neural progenitor proliferation in the ventricular zone (Chenn and Walsh, 2002; Zechner et al, 2003; Zechner and Bailey, 2004; Kalani et al, 2008). Wnt/β-catenin signaling is required for NPC differentiation in neurons (Hirabayashi et al, 2004; Otero et al, 2004; Lie et al, 2005; Lyashenko et al, 2011); more recent studies show that inhibition of the Wnt/β-catenin pathway promotes neuronal differentiation in the intermediate zone of the dorsal neural tube (Xie et al, 2011). The Wnt/β-catenin signal seems to be essential both to control the size of the progenitor pool and to impinge on the fate of neuronal progenitors, to either proliferate or differentiate
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