Secreted proteoglycan molecule Tsukushi (TSK) regulates various developmental processes, such as early body patterning and neural plate formation by interacting with major signaling pathways like Wnt, BMP, Notch etc. In central nervous system, TSK inhibits Wnt signaling to control chick retinal development. It also plays important roles for axon guidance and anterior commissure formation in mouse brain. In the present study, we investigated the role of TSK for the development and proper functioning of mouse hippocampus. We found that TSK expression is prominent at hippocampal regions of early postnatal mouse until postnatal day 15 and gradually declines at later stages. Hippocampal dimensions are affected in TSK knockout mice (TSK-KO) as shown by reduced size of hippocampus and dentate gyrus (DG). Interestingly, neural stem cell (NSC) density at the neural niche of DG was higher in TSK-KO compared with wild-type. The ratio of proliferating NSCs as well as the rate of overall cell proliferation was also higher in TSK-KO hippocampus. Our in vitro study also suggests an increased number of neural stem/progenitor cells residing in TSK-KO hippocampus. Finally, we found that the terminal differentiation of NSCs in TSK-KO was disturbed as the differentiation to neuronal cell lineage was increased while the percentages of astrocytes and oligodendrocytes were decreased. Overall, our study establishes the involvement of TSK in hippocampal development, NSC maintenance and terminal differentiation at perinatal stages.

中文翻译：

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筑紫对于小鼠海马神经干细胞的正确维持和终末分化至关重要。

分泌的蛋白聚糖分子Tsukushi（TSK）通过与Wnt，BMP，Notch等主要信号传导途径相互作用，调节各种发育过程，例如早期人体构图和神经板形成。在中枢神经系统中，TSK抑制Wnt信号传导以控制雏鸡视网膜发育。它还在小鼠脑中轴突引导和前连合形成中起重要作用。在本研究中，我们调查了TSK在小鼠海马的发育和正常功能中的作用。我们发现，TSK表达在出生后早期的小鼠海马区域突出，直到出生后第15天，并在以后的阶段逐渐下降。TSK基因敲除小鼠（TSK-KO）的海马尺寸受到影响，如海马和齿状回（DG）的大小减小所显示。有趣的是 与野生型相比，TSK-KO中DG神经位处的神经干细胞（NSC）密度更高。在TSK-KO海马中，增殖的NSC的比例以及总体细胞增殖的速率也更高。我们的体外研究还表明，存在于TSK-KO海马中的神经干/祖细胞数量增加。最后，我们发现，随着向神经元细胞谱系分化的增加而星形胶质细胞和少突胶质细胞的百分比降低，NSCs在TSK-KO中的终末分化受到干扰。总体而言，我们的研究确定了TSK在围产期阶段参与海马发育，NSC维持和终末分化。在TSK-KO海马中，增殖的NSC的比例以及总体细胞增殖的速率也更高。我们的体外研究还表明，存在于TSK-KO海马中的神经干/祖细胞数量增加。最后，我们发现，随着向神经元细胞谱系分化的增加而星形胶质细胞和少突胶质细胞的百分比降低，NSCs在TSK-KO中的终末分化受到干扰。总体而言，我们的研究确定了TSK在围产期阶段参与海马发育，NSC维持和终末分化。在TSK-KO海马中，增殖的NSC的比例以及总体细胞增殖的速率也更高。我们的体外研究还表明，存在于TSK-KO海马中的神经干/祖细胞数量增加。最后，我们发现，随着向神经元细胞谱系分化的增加而星形胶质细胞和少突胶质细胞的百分比降低，NSCs在TSK-KO中的终末分化受到干扰。总体而言，我们的研究确定了TSK在围产期阶段参与海马发育，NSC维持和终末分化。我们发现，随着向神经元细胞谱系分化的增加，星形胶质细胞和少突胶质细胞的百分比降低，NSCs在TSK-KO中的终末分化受到干扰。总体而言，我们的研究确定了TSK在围产期阶段参与海马发育，NSC维持和终末分化。我们发现，随着向神经元细胞谱系分化的增加，星形胶质细胞和少突胶质细胞的百分比降低，NSCs在TSK-KO中的终末分化受到干扰。总体而言，我们的研究确定了TSK在围产期阶段参与海马发育，NSC维持和终末分化。