Nyfeler Yves, Kirch Robert D, Mantei Ned, Leone Dino P, Radtke Freddy, Suter Ueli, Taylor Verdon
Department of Molecular Embryology, Max-Planck Institute of Immunobiology, Freiburg, Germany.
EMBO J. 2005 Oct 5;24(19):3504-15. doi: 10.1038/sj.emboj.7600816. Epub 2005 Sep 15.
Neural stem cells (NSCs) in the postnatal mammalian brain self-renew and are a source of neurons and glia. To date, little is known about the molecular and cellular mechanisms regulating the maintenance and differentiation of these multipotent progenitors. We show that Jagged1 is required by mitotic cells in the subventricular zone (SVZ) and stimulates self-renewal of multipotent epidermal growth factor-dependent NSCs. Jagged1-expressing cells line the adult SVZ and are juxtaposed to Notch1-expressing cells, some of which are putative NSCs. In vitro, endogenous Jagged1 acts through Notch1 to promote NSC maintenance and multipotency. In vivo, reducing Jagged1/Notch1 signaling decreases the number of proliferating cells in the SVZ. In addition, soluble Jagged1 promotes self-renewal and neurogenic potential of multipotent neural progenitors in vitro. Our findings suggest a central role for Jagged1 in the NSC niche in the SVZ for maintaining a population of NSCs in the postnatal brain.
出生后哺乳动物大脑中的神经干细胞（NSCs）能够自我更新，是神经元和神经胶质细胞的来源。迄今为止，对于调节这些多能祖细胞维持和分化的分子及细胞机制知之甚少。我们发现，室下区（SVZ）的有丝分裂细胞需要Jagged1，并刺激多能表皮生长因子依赖型神经干细胞的自我更新。表达Jagged1的细胞排列在成年SVZ中，并与表达Notch1的细胞相邻，其中一些是假定的神经干细胞。在体外，内源性Jagged1通过Notch1发挥作用，以促进神经干细胞的维持和多能性。在体内，降低Jagged1/Notch1信号会减少SVZ中增殖细胞的数量。此外，可溶性Jagged1在体外可促进多能神经祖细胞的自我更新和神经发生潜能。我们的研究结果表明，Jagged1在SVZ的神经干细胞生态位中对于维持出生后大脑中的神经干细胞群体起着核心作用。
