Department of Psychiatry and Behavioral Sciences, School of Medicine, UC Davis, Sacramento, CA, USA.
Neuroscience Graduate Program, UC Davis, Davis, CA, USA.
Cereb Cortex. 2019 Jul 5;29(7):2782-2796. doi: 10.1093/cercor/bhy145.
Microglial cells are increasingly recognized as modulators of brain development. We previously showed that microglia colonize the cortical proliferative zones in the prenatal brain and regulate the number of precursor cells through phagocytosis. To better define cellular interactions between microglia and proliferative cells, we performed lentiviral vector-mediated intraventricular gene transfer to induce enhanced green fluorescent protein expression in fetal cerebrocortical cells. Tissues were collected and counterstained with cell-specific markers to label microglial cells and identify other cortical cell types. We found that microglial cells intimately interact with the radial glial scaffold and make extensive contacts with neural precursor cells throughout the proliferative zones, particularly in the rhesus monkey fetus when compared to rodents. We also identify a subtype of microglia, which we term 'periventricular microglia', that interact closely with mitotic precursor cells in the ventricular zone. Our data suggest that microglia are structural modulators that facilitate remodeling of the proliferative zones as precursor cells migrate away from the ventricle and may facilitate the delamination of precursor cells. Taken together, these results indicate that microglial cells are an integral component of cortical proliferative zones and contribute to the interactive milieu in which cortical precursor cells function.
小胶质细胞越来越被认为是大脑发育的调节者。我们之前的研究表明,小胶质细胞在胚胎大脑的皮质增殖区定殖,并通过吞噬作用调节前体细胞的数量。为了更好地定义小胶质细胞与增殖细胞之间的细胞相互作用,我们进行了慢病毒载体介导的脑室基因转移,以诱导胎脑皮质细胞中增强型绿色荧光蛋白的表达。收集组织并用细胞特异性标志物进行复染,以标记小胶质细胞并鉴定其他皮质细胞类型。我们发现小胶质细胞与放射状胶质支架密切相互作用,并与整个增殖区的神经前体细胞广泛接触,在恒河猴胎儿中与啮齿动物相比更为明显。我们还鉴定出一种小胶质细胞亚型,我们称之为“室周小胶质细胞”,它与室管膜区的有丝分裂前体细胞密切相互作用。我们的数据表明,小胶质细胞是结构调节剂,可促进前体细胞从脑室迁移时增殖区的重塑,并可能促进前体细胞的分层。综上所述,这些结果表明小胶质细胞是皮质增殖区的一个组成部分,并有助于皮质前体细胞发挥功能的相互作用环境。