Galectin-3 maintains cell motility from the subventricular zone to the olfactory bulb
Galectin-3 maintains cell motility from the subventricular zone to the olfactory bulb
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DOI：
10.1242/jcs.079954
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发表时间：
2011-07-15
影响因子：
4
通讯作者：
Szele, Francis G.
中科院分区：
文献类型：
--
作者：
Comte, Isabelle;Kim, Yongsoo;Szele, Francis G.
成人大脑室下区 (SVZ) 产生神经母细胞，这些神经母细胞通过头端迁移流 (RMS) 迁移到特定生态位中的嗅球 (OB)。 Galectin-3 (Gal-3) 调节癌症的增殖和迁移，并由脑损伤后激活的巨噬细胞表达。 Gal-3在正常大脑中的功能尚不清楚，但我们偶然发现它在未受伤小鼠的室管膜细胞和SVZ星形胶质细胞中表达。室管膜纤毛建立趋化梯度，星形胶质细胞形成神经胶质管，它们结合起来有助于神经母细胞迁移。整体制备和电子显微镜显示 Gal3(-/-) 小鼠的室管膜纤毛和 SVZ 星形胶质细胞均被破坏。有趣的是，标记后两周，Gal3(-/-) 小鼠的 OB 中发现的新 BrdU(+) 神经元比野生型小鼠少得多。然而，SVZ 增殖和细胞死亡以及 OB 分化率未改变。这表明体内迁移的减少足以减少新 OB 神经元的数量。前脑切片的双光子延时显微镜证实迁移减少； Gal3(-/-) 小鼠的细胞速度较慢且更具探索性。 Gal-3 阻断抗体减少了迁移并分离了神经母细胞-细胞接触，而重组 Gal-3 则增加了外植体的迁移。最后，我们发现 Gal3(-/-) 小鼠中磷酸化表皮生长因子受体 (EGFR) 的表达增加。这些结果表明，Gal-3 在 SVZ 神经母细胞迁移中很重要，可能是通过基于 EGFR 的机制，并揭示了这种凝集素在未受伤大脑中的作用。
The adult brain subventricular zone (SVZ) produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB) in a specialized niche. Galectin-3 (Gal-3) regulates proliferation and migration in cancer and is expressed by activated macrophages after brain injury. The function of Gal-3 in the normal brain is unknown, but we serendipitously found that it was expressed by ependymal cells and SVZ astrocytes in uninjured mice. Ependymal cilia establish chemotactic gradients and astrocytes form glial tubes, which combine to aid neuroblast migration. Whole-mount preparations and electron microscopy revealed that both ependymal cilia and SVZ astrocytes were disrupted in Gal3(-/-) mice. Interestingly, far fewer new BrdU(+) neurons were found in the OB of Gal3(-/-) mice, than in wild-type mice 2 weeks after labeling. However, SVZ proliferation and cell death, as well as OB differentiation rates were unaltered. This suggested that decreased migration in vivo was sufficient to decrease the number of new OB neurons. Two-photon time-lapse microscopy in forebrain slices confirmed decreased migration; cells were slower and more exploratory in Gal3(-/-) mice. Gal-3 blocking antibodies decreased migration and dissociated neuroblast cell-cell contacts, whereas recombinant Gal-3 increased migration from explants. Finally, we showed that expression of phosphorylated epidermal growth factor receptor (EGFR) was increased in Gal3(-/-) mice. These results suggest that Gal-3 is important in SVZ neuroblast migration, possibly through an EGFR-based mechanism, and reveals a role for this lectin in the uninjured brain.