Akhirin regulates the proliferation and differentiation of neural stem cells in intact and injured mouse spinal cord

Abstract

Although the central nervous system is considered a comparatively static tissue with limited cell turnover, cells with stem cell properties have been isolated from most neural tissues. The spinal cord ependymal cells show neural stem cell potential in vitro and in vivo in injured spinal cord. However, very little is known regarding the ependymal niche in the mouse spinal cord. We previously reported that a secreted factor, chick Akhirin, is expressed in the ciliary marginal zone of the eye, where it works as a heterophilic cell-adhesion molecule. Here, we describe a new crucial function for mouse Akhirin (M-AKH) in regulating the proliferation and differentiation of progenitors in the mouse spinal cord. During embryonic spinal cord development, M-AKH is transiently expressed in the central canal ependymal cells, which possess latent neural stem cell properties. Targeted inactivation of the AKH gene in mice causes a reduction in the size of the spinal cord and decreases BrdU incorporation in the spinal cord. Remarkably, the expression patterns of ependymal niche molecules in AKH knockout (AKH-/-) mice are different from those of AKH+/+, both in vitro and in vivo. Furthermore, we provide evidence that AKH expression in the central canal is rapidly upregulated in the injured spinal cord. Taken together, these results indicate that M-AKH plays a crucial role in mouse spinal cord formation by regulating the ependymal niche in the central canal.

Transcriptome analysis identifies genes involved with the development of umbilical hernias in pigs

“…VIT is responsible for encoding a protein related to the ECM and also participates in cell adhesion and cell migration [54,55]. The vitrin protein is similar to proteins that participate in the neural development and in the integrity of the extracellular matrix [56][57][58]. In the intact human cartilaginous tissues, higher levels of VIT were observed, whereas in tissues with cartilage problems the expression of this gene was reduced [59].…”

Common Genetic Variant in VIT Is Associated with Human Brain Asymmetry

“…Also vitrin displays high homology and structural similarity to Akhirin and cochlin (Ahsan et al, 2005 ). Both Akhirin and cochlin are involved in neural development and extracellular matrix integrity (Zhang et al, 2013 ; Bae et al, 2014 ; Abdulhaleem et al, 2015 ). These structural similarities suggest the possible role of vitrin in matrix assembly, cell adhesion, and migration, processes that are crucial for neural development.…”

Akhirin regulates the proliferation and differentiation of neural stem cells/progenitor cells at neurogenic niches in mouse brain

“…AKH has a high homology with mouse vitrin and chicken cochlin, and shows heterophilic cell adhesion property. Later we found its role on NSC proliferation and differentiation in the development as well as its maintenance role in the injury condition of mouse spinal cord (Abdulhaleem et al, ; Acharjee et al, ). Now we report that AKH acts as a pivotal factor in the regulation of NSC/NPC during the SVZ and the hippocampal neurogenesis.…”

“…All animal experiments were conducted according to the guidelines of Animal Research: In Vivo Experiment Report (ARRIVE) (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010). The generation of AKH knockout mice (AKH −/− ) has been described previously (Abdulhaleem et al, 2015). All mice were maintained in a mixed C57BL/6 strain background and both sexes of mice were used for this experimental purpose.…”

“…Experimental procedures for in situ hybridization (ISH) were described before (Abdulhaleem et al, 2015;Ahsan et al, 2005). In brief, from corresponding DNA construct digoxigenin-labeled antisense probe for AKH coding region was produced.…”