Tawarayama Hiroshi, Yamada Hirohisa, Amin Ruhul, Morita-Fujimura Yuiko, Cooper Helen M, Shinmyo Yohei, Tanaka Hideaki, Ikawa Shuntaro
Department of Developmental Neurobiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan; Department of Project Programs, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai 980-8575, Japan; Department of Ecology and Evolutionary Biology, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan.
Department of Developmental Neurobiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Neuroscience. 2020 Apr 1;431:184-192. doi: 10.1016/j.neuroscience.2020.02.005. Epub 2020 Feb 18.
The hippocampus is characterized by the presence of life-long neurogenesis. To elucidate the molecular mechanism regulating hippocampal neurogenesis, we studied the functions of the chemorepellent Draxin in neuronal proliferation and differentiation in the postnatal dentate gyrus. The present in vivo cell labeling and fate tracking analyses revealed enhanced differentiation of hippocampal neural stem and progenitor cells (hNSPCs) in the subgranular zone (SGZ) of Draxin-deficient mice. We observed a reduction in the number of BrdU-pulse labeled or Ki-67 immunopositive SGZ cells in the mutant mice. However, Draxin deficiency did not affect cell cycle duration of SGZ cells. In situ hybridization analysis indicated that the receptor component of the canonical Wnt pathway, Lrp6, is expressed in SGZ cells, including Nestin and Sox2 double-positive hNSPCs. Taken together with the previous finding that Draxin interacts physically with Lrp6, we postulate that Draxin plays a pivotal role in the regulation of Wnt-driven hNSPC differentiation to modulate the rate of neuronal differentiation in the progenitor population.
海马体的特征是存在终生神经发生。为了阐明调节海马体神经发生的分子机制，我们研究了化学排斥分子Draxin在出生后齿状回神经元增殖和分化中的作用。目前的体内细胞标记和命运追踪分析显示，Draxin基因缺陷小鼠颗粒下区（SGZ）的海马神经干细胞和祖细胞（hNSPCs）的分化增强。我们观察到突变小鼠中BrdU脉冲标记或Ki-67免疫阳性的SGZ细胞数量减少。然而，Draxin缺乏并不影响SGZ细胞的细胞周期持续时间。原位杂交分析表明，经典Wnt信号通路的受体成分Lrp6在SGZ细胞中表达，包括巢蛋白和Sox2双阳性的hNSPCs。结合之前Draxin与Lrp6发生物理相互作用的发现，我们推测Draxin在Wnt驱动的hNSPC分化调节中起关键作用，以调节祖细胞群中神经元分化的速率。
