Nguyen-Ba-Charvet Kim T, Picard-Riera Nathalie, Tessier-Lavigne Marc, Baron-Van Evercooren Anne, Sotelo Constantino, Chédotal Alain
Institut National de la Santé et de la Recherche Médicale U106, Bâtiment de Pédiatrie, Hôpital de la Salpêtrière, 75013 Paris, France.
J Neurosci. 2004 Feb 11;24(6):1497-506. doi: 10.1523/JNEUROSCI.4729-03.2004.
The subventricular zone (SVZ) contains undifferentiated cells, which proliferate and generate olfactory bulb (OB) interneurons. Throughout life, these cells leave the SVZ and migrate along the rostral migratory stream (RMS) to the OB where they differentiate. In vitro, the septum and the choroid plexus (CP) secrete repulsive factors that could orient the migration of OB precursors. Slit1 and Slit2, two known chemorepellents for developing axons, can mimic this effect. We show here that the Slit receptors Robo2 and Robo3/Rig-1 are expressed in the SVZ and the RMS and that Slit1 and Slit2 are still present in the adult septum. Using Slit1/2-deficient mice, we found that Slit1 and Slit2 are responsible for both the septum and the CP repulsive activity in vitro. In adult mice lacking Slit1, small chains of SVZ-derived cells migrate caudally into the corpus callosum, supporting a role for Slits in orienting the migration of SVZ cells. Surprisingly, in adult mice, Slit1 was also expressed by type A and type C cells in the SVZ and RMS, suggesting that Slit1 could act cell autonomously. This hypothesis was tested using cultures of SVZ explants or isolated neurospheres from Slit1-/- or Slit1+/- mice. In both types of cultures, the migration of SVZ cells was altered in the absence of Slit1. This suggests that the regulation of the migration of OB precursors by Slit proteins is complex and not limited to repulsion.
脑室下区（SVZ）含有未分化细胞，这些细胞增殖并产生嗅球（OB）中间神经元。在整个生命过程中，这些细胞离开SVZ并沿着吻侧迁移流（RMS）迁移到OB，在那里它们分化。在体外，隔膜和脉络丛（CP）分泌可引导OB前体细胞迁移的排斥因子。Slit1和Slit2是两种已知的轴突发育化学排斥剂，可模拟这种作用。我们在此表明，Slit受体Robo2和Robo3/Rig-1在SVZ和RMS中表达，且Slit1和Slit2仍存在于成年隔膜中。使用Slit1/2基因敲除小鼠，我们发现Slit1和Slit2在体外对隔膜和CP的排斥活性均起作用。在缺乏Slit1的成年小鼠中，SVZ来源的细胞小链向尾侧迁移进入胼胝体，这支持了Slits在引导SVZ细胞迁移中的作用。令人惊讶的是，在成年小鼠中，Slit1在SVZ和RMS的A型和C型细胞中也有表达，这表明Slit1可能以细胞自主方式发挥作用。使用来自Slit1-/-或Slit1+/-小鼠的SVZ外植体培养物或分离的神经球对这一假设进行了验证。在这两种培养类型中，缺乏Slit1时SVZ细胞的迁移均发生改变。这表明Slit蛋白对OB前体细胞迁移的调节是复杂的，且不限于排斥作用。
