Conover J C, Doetsch F, Garcia-Verdugo J M, Gale N W, Yancopoulos G D, Alvarez-Buylla A
The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Nat Neurosci. 2000 Nov;3(11):1091-7. doi: 10.1038/80606.
The subventricular zone (SVZ) of the lateral ventricles, the largest remaining germinal zone of the adult mammalian brain, contains an extensive network of neuroblasts migrating rostrally to the olfactory bulb. Little is known about the endogenous proliferation signals for SVZ neural stem cells or guidance cues along the migration pathway. Here we show that the receptor tyrosine kinases EphB1-3 and EphA4 and their transmembrane ligands, ephrins-B2/3, are expressed by cells of the SVZ. Electron microscopy revealed ephrin-B ligands associated with SVZ astrocytes, which function as stem cells in this germinal zone. A three-day infusion of the ectodomain of either EphB2 or ephrin-B2 into the lateral ventricle disrupted migration of neuroblasts and increased cell proliferation. These results suggest that Eph/ephrin signaling is involved in the migration of neuroblasts in the adult SVZ and in either direct or indirect regulation of cell proliferation.
侧脑室的室下区（SVZ）是成年哺乳动物大脑中现存最大的生发区，其中含有广泛的神经母细胞网络，这些神经母细胞向嗅球呈头端迁移。关于SVZ神经干细胞的内源性增殖信号或迁移途径中的引导线索，人们所知甚少。在这里，我们表明受体酪氨酸激酶EphB1 - 3和EphA4及其跨膜配体ephrin - B2/3由SVZ的细胞表达。电子显微镜显示ephrin - B配体与SVZ星形胶质细胞相关，而星形胶质细胞在这个生发区发挥干细胞的作用。将EphB2或ephrin - B2的胞外域注入侧脑室三天，会破坏神经母细胞的迁移并增加细胞增殖。这些结果表明，Eph/ephrin信号传导参与成年SVZ中神经母细胞的迁移以及细胞增殖的直接或间接调节。
