Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, CEP 21941-902, Brazil.
Cereb Cortex. 2010 Oct;20(10):2411-22. doi: 10.1093/cercor/bhp309. Epub 2010 Jan 13.
Chondroitin sulfate (CS) carrying proteoglycans (PGs) are widely expressed in the nervous system, and there is increasing evidence that they regulate developmental mechanisms like neurite outgrowth, axonal guidance and neuronal migration. Moreover, they can also act indirectly by organizing and/or modulating growth factors and guidance molecules. We found that chondroitin-4-sulfate is coexpressed with semaphorin 3A (Sema 3A) in the striatal mantle zone (SMZ), a nontarget region of neuropilin (Nrp)-1-expressing cortical interneurons flanking their migratory route in the subpallium. Using in vitro assays, we showed that CS PGs exert a repulsive effect on cortical interneurons, independently of Sema 3A, due to the CS side chains. We further showed that extracellular Sema 3A binds to CS. Disrupting Sema 3A-Nrp-1 signaling led migrating medial ganglionic eminence neurons to inappropriately invade the SMZ and even more so after removal of the CS side chains. Moreover, we found that soluble Sema 3A enhances the CS-induced repulsion in vitro. We concluded that CS acts as a repellent for cortical interneurons and that, in addition, CS restricts secreted Sema 3A within SMZ. Thus, both molecules act in concert to repel cortical interneurons from the SMZ during tangential migration toward the cerebral cortex.
硫酸软骨素（CS）携带蛋白聚糖（PGs）广泛表达于神经系统，越来越多的证据表明它们调控神经突生长、轴突导向和神经元迁移等发育机制。此外，它们还可以通过组织和/或调节生长因子和导向分子间接发挥作用。我们发现硫酸软骨素 4-硫酸盐（chondroitin-4-sulfate）与神经纤毛蛋白 1（Nrp-1）表达的皮质中间神经元迁移路径侧翼纹状体帽状区（striatal mantle zone，SMZ）中的 Sema3A 共表达。通过体外实验，我们发现 CS PGs 对皮质中间神经元具有排斥作用，这种作用不依赖于 Sema3A，而是由于 CS 侧链。我们进一步表明细胞外 Sema3A 与 CS 结合。破坏 Sema3A-Nrp-1 信号导致迁移的内侧神经节隆起神经元异常侵入 SMZ，且 CS 侧链去除后这种侵入更为明显。此外，我们发现可溶性 Sema3A 增强了 CS 诱导的体外排斥反应。综上，我们得出结论，CS 作为皮质中间神经元的排斥物，此外，CS 将分泌型 Sema3A 限制在 SMZ 内。因此，这两种分子在皮质中间神经元向大脑皮层进行切线迁移的过程中协同作用，将其排斥出 SMZ。
