Inta Dragos, Alfonso Julieta, von Engelhardt Jakob, Kreuzberg Maria M, Meyer Axel H, van Hooft Johannes A, Monyer Hannah
Department of Clinical Neurobiology, Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20994-9. doi: 10.1073/pnas.0807059105. Epub 2008 Dec 18.
Most forebrain GABAergic interneurons in rodents are born during embryonic development in the ganglionic eminences (GE) and migrate tangentially into the cortical plate. A subset, however, continues to be generated postnatally in the subventricular zone (SVZ). These interneurons populate the olfactory bulb (OB) reached via migration in the rostral migratory stream (RMS). Employing transgenic mice expressing EGFP in 5-HT(3)-positive neurons, we identified additional migratory pathways in the early postnatal brain. Time-lapse imaging experiments revealed massive migration of EGFP-positive cells from the SVZ into numerous forebrain regions, including cortex, striatum, and nucleus accumbens. The neuronal fate of the migratory EGFP-labeled cells was indicated by their doublecortin (DCX) expression. Birthdating experiments, by using 5-bromo-2'-deoxyuridine (BrdU) and retrovirus-based experiments, provided evidence that migrating neuroblasts were born in the SVZ postnatally and developed a distinct GABAergic phenotype. Our results demonstrate that the SVZ is a reservoir of GABAergic interneurons not only for the OB, but also for other cortical and subcortical areas.
啮齿动物的大多数前脑γ-氨基丁酸能中间神经元在胚胎发育期间于神经节隆起(GE)中产生,并沿切线方向迁移至皮质板。然而,有一部分神经元在出生后继续在脑室下区(SVZ)产生。这些中间神经元通过在吻侧迁移流(RMS)中的迁移进入嗅球(OB)。利用在5-羟色胺(3)阳性神经元中表达增强绿色荧光蛋白(EGFP)的转基因小鼠,我们在出生后早期的大脑中发现了其他迁移途径。延时成像实验显示,EGFP阳性细胞大量从SVZ迁移至包括皮质、纹状体和伏隔核在内的众多前脑区域。迁移的EGFP标记细胞的神经元命运通过其双皮质素(DCX)表达得以表明。利用5-溴-2'-脱氧尿苷(BrdU)进行的出生时间标记实验以及基于逆转录病毒的实验证明,迁移的神经母细胞在出生后于SVZ产生,并发育出独特的γ-氨基丁酸能表型。我们的结果表明,SVZ不仅是OB的γ-氨基丁酸能中间神经元的储备库,也是其他皮质和皮质下区域的储备库。