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

Specialized microenvironment, or neurogenic niche, in embryonic and postnatal mouse brain plays critical roles during neurogenesis throughout adulthood. The subventricular zone (SVZ) and the dentate gyrus (DG) of hippocampus in the mouse brain are two major neurogenic niches where neurogenesis is directed by numerous regulatory factors. Now, we report Akhirin (AKH), a stem cell maintenance factor in mouse spinal cord, plays a pivotal regulatory role in the SVZ and in the DG. AKH showed specific distribution during development in embryonic and postnatal neurogenic niches. Loss of AKH led to abnormal development of the ventricular zone and the DG along with reduction of cellular proliferation in both regions. In AKH knockout mice (AKH-/- ), quiescent neural stem cells (NSCs) increased, while proliferative NSCs or neural progenitor cells decreased at both neurogenic niches. In vitro NSC culture assay showed increased number of neurospheres and reduced neurogenesis in AKH-/- . These results indicate that AKH, at the neurogenic niche, exerts dynamic regulatory role on NSC self-renewal, proliferation and differentiation during SVZ and hippocampal neurogenesis.

Tsukushi expression is dependent on Notch signaling and oscillated in the presomitic mesoderm during chick somitogenesis.

During somitogenesis, segmentation of the body axis occurs by epithelial somites budding off from the rostral end of the unsegmented presomitic mesoderm (PSM), and its molecular regulation is achieved by a molecular oscillator and signaling molecules. Tsukushi (TSK) is a unique secreted protein and involved in diverse biological cascades in vertebrate embryos by modulating several signaling pathways at the extracellular region. However, the involvement of TSK in somitogenesis remains unknown. In this study, we investigated the detailed expression patterns of TSK at different developmental stages of a chick embryo. Chick-TSK (C-TSK) is expressed in the PSM and shows an oscillation pattern with three phases. The oscillation pattern of C-TSK in the PSM is similar to that of c-Notch1 and c-hairy1, but not to c-Delta1. Our in vitro data showed that Notch signaling is necessary for the normal expression of C-TSK and that expression of C-TSK is an intrinsic property of the anterior PSM. These data suggest that TSK plays a role in chick somitogenesis.