Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, USA.
Glia. 2011 Nov;59(11):1579-87. doi: 10.1002/glia.21199. Epub 2011 Jun 14.
Neurogenesis in the post-natal brain occurs in two primary locations: the subgranular layer of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles. Following differentiation, neuroblasts within the SVZ migrate several millimeters to the olfactory bulbs (OBs) via a distinct anatomic route, or rostral migratory stream (RMS). The genes that govern neuroblast directional migration, and particularly those encoding cell adhesion and signaling factors, remain largely uncharacterized. Here, we report that the extracellular matrix adhesion receptor, β8 integrin, is essential for proper neuroblast chain formation and directional navigation in the RMS. Primary neuroblasts isolated from the mouse brain express robust levels of β8 integrin protein, and selective ablation of β8 integrin gene expression in neuroblasts leads to aberrant chain migration and size-reduced OBs. These integrin-dependent defects can be recapitulated ex vivo using isolated neurospheres or SVZ explants. Collectively, these data identify essential cell-intrinsic functions for β8 integrin in regulating neuroblast polarity and directional navigation in the mouse forebrain.
海马齿状回的颗粒下层和侧脑室的室下区 (SVZ)。分化后，SVZ 中的神经前体细胞通过独特的解剖途径——即前迁移流 (RMS)——迁移到几个毫米远处的嗅球 (OB)。支配神经前体细胞定向迁移的基因，特别是那些编码细胞黏附和信号因子的基因，在很大程度上仍未被描述。在这里，我们报告细胞外基质黏附受体β8 整合素对于 RMS 中神经前体细胞的正确链形成和定向导航是必需的。从小鼠脑中分离的原代神经前体细胞表达高水平的β8 整合素蛋白，而选择性敲除神经前体细胞中的β8 整合素基因表达会导致异常的链迁移和 OB 体积减小。这些整合素依赖性缺陷可以使用分离的神经球或 SVZ 外植体在体外重现。总的来说，这些数据确定了β8 整合素在调节小鼠前脑神经前体细胞极性和定向导航中的内在细胞功能。
