Interdepartmental Neuroscience Program, Northwestern University, Chicago, Illinois, United States of America.
PLoS One. 2009 Dec 2;4(12):e8122. doi: 10.1371/journal.pone.0008122.
The adult subventricular zone (SVZ) contains stem and progenitor cells that generate neuroblasts throughout life. Although it is well accepted that SVZ neuroblasts are migratory, recent evidence suggests their progenitor cells may also exhibit motility. Since stem and progenitor cells are proliferative and multipotential, if they were also able to move would have important implications for SVZ neurogenesis and its potential for repair.
METHODOLOGY/PRINCIPAL FINDINGS: We studied whether SVZ stem and/or progenitor cells are motile in transgenic GFP+ slices with two photon time lapse microscopy and post hoc immunohistochemistry. We found that stem and progenitor cells; mGFAP-GFP+ cells, bright nestin-GFP+ cells and Mash1+ cells were stationary in the SVZ and rostral migratory stream (RMS). In our search for motile progenitor cells, we uncovered a population of motile betaIII-tubulin+ neuroblasts that expressed low levels of epidermal growth factor receptor (EGFr). This was intriguing since EGFr drives proliferation in the SVZ and affects migration in other systems. Thus we examined the potential role of EGFr in modulating SVZ migration. Interestingly, EGFr(low) neuroblasts moved slower and in more tortuous patterns than EGFr-negative neuroblasts. We next questioned whether EGFr stimulation affects SVZ cell migration by imaging Gad65-GFP+ neuroblasts in the presence of transforming growth factor alpha (TGF-alpha), an EGFr-selective agonist. Indeed, acute exposure to TGF-alpha decreased the percentage of motile cells by approximately 40%.
CONCLUSIONS/SIGNIFICANCE: In summary, the present study directly shows that SVZ stem and progenitor cells are static, that EGFr is retained on some neuroblasts, and that EGFr stimulation negatively regulates migration. This result suggests an additional role for EGFr signaling in the SVZ.
成年侧脑室下区（SVZ）含有干细胞和祖细胞，它们在整个生命过程中产生神经母细胞。虽然 SVZ 神经母细胞是迁移性的这一点已被广泛接受，但最近的证据表明，它们的祖细胞也可能具有运动性。由于干细胞和祖细胞具有增殖和多能性，如果它们也能够移动，将对 SVZ 神经发生及其修复潜力产生重要影响。
方法/主要发现：我们使用双光子延时显微镜和事后免疫组织化学研究了 SVZ 干细胞和/或祖细胞是否具有迁移能力。我们发现，干细胞和祖细胞；mGFAP-GFP+细胞、亮nestin-GFP+细胞和 Mash1+细胞在 SVZ 和前迁移流（RMS）中是静止的。在我们寻找运动性祖细胞的过程中，我们发现了一群表达低水平表皮生长因子受体（EGFr）的运动性βIII-微管蛋白+神经母细胞。这很有趣，因为 EGFr 驱动 SVZ 中的增殖，并影响其他系统中的迁移。因此，我们研究了 EGFr 在调节 SVZ 迁移中的潜在作用。有趣的是，EGFr(low)神经母细胞的运动速度较慢，运动轨迹也较曲折，而 EGFr 阴性神经母细胞则较快且运动轨迹较直。接下来，我们通过在转化生长因子α（TGF-α）存在的情况下对 Gad65-GFP+神经母细胞进行成像，来询问 EGFr 刺激是否会影响 SVZ 细胞迁移。事实上，急性暴露于 TGF-α会使大约 40%的运动细胞数量减少。
结论/意义：总之，本研究直接表明 SVZ 干细胞和祖细胞是静止的，一些神经母细胞上保留有 EGFr，并且 EGFr 刺激负调节迁移。这一结果表明 EGFr 信号在 SVZ 中具有额外的作用。
