Aguirre Adan, Gallo Vittorio
Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
J Neurosci. 2004 Nov 17;24(46):10530-41. doi: 10.1523/JNEUROSCI.3572-04.2004.
We used a 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein (EGFP) transgenic mouse to study postnatal subventricular zone (SVZ) progenitor fate, with a focus on the olfactory bulb (OB). The postnatal OB of the CNP-EGFP mouse contained EGFP+ interneurons and oligodendrocytes. In the anterior SVZ, the majority of EGFP+ progenitors were NG2+. These NG2+/EGFP+ progenitors expressed the OB interneuron marker Er81, the neuroblast markers doublecortin (DC) and Distalless-related homeobox (DLX), or the oligodendrocyte progenitor marker Nkx2.2. In the rostral migratory stream (RMS), EGFP+ cells displayed a migrating phenotype. A fraction of these cells were either NG2-/Er81+/DC+/DLX+ or NG2+/Nkx2.2+. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) injection into the lateral ventricle (LV) of early postnatal mice demonstrated that NG2+/EGFP+ progenitors migrate from the SVZ through the RMS into the OB. Moreover, fluorescence-activated cell-sorting-purified NG2+/CNP-EGFP+ or NG2+/beta-actin-enhanced yellow fluorescent protein-positive (EYFP+) progenitors transplanted into the early postnatal LV displayed extensive rostral and caudal migration. EYFP+ or EGFP+ graft-derived cells within the RMS were DLX+/Er81+ or Nkx2.2+, migrated to the OB, and differentiated to interneurons and oligodendrocytes. In the subcortical white matter (SCWM), grafted cells differentiated to either oligodendrocytes or astrocytes. Transplantation of NG2+/EYFP+ progenitors selectively purified from the SVZ showed that these cells were migratory and generated glia and neurons in the OB, hippocampus, and striatum. In contrast, cortical, OB, or cerebellar NG2+ cells had a very limited migratory potential and gave rise to glia in the SCWM and striatum. Our findings indicate region-specific differences between NG2+ progenitor cells and show that NG2+ cells can migrate throughout the RMS and contribute to both gliogenesis and neurogenesis in the postnatal OB.
我们使用了一种2',3'-环核苷酸3'-磷酸二酯酶（CNP）增强型绿色荧光蛋白（EGFP）转基因小鼠来研究出生后室下区（SVZ）祖细胞的命运，重点是嗅球（OB）。CNP-EGFP小鼠出生后的嗅球含有EGFP+中间神经元和少突胶质细胞。在前部SVZ，大多数EGFP+祖细胞为NG2+。这些NG2+/EGFP+祖细胞表达嗅球中间神经元标志物Er81、成神经细胞标志物双皮质素（DC）和远端相关同源盒（DLX），或少突胶质细胞祖细胞标志物Nkx2.2。在吻侧迁移流（RMS）中，EGFP+细胞呈现迁移表型。这些细胞中的一部分要么是NG2-/Er81+/DC+/DLX+，要么是NG2+/Nkx2.2+。对出生后早期小鼠侧脑室（LV）注射DiI（1,1'-二硬脂酰基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐）表明，NG2+/EGFP+祖细胞从SVZ通过RMS迁移到OB。此外，荧光激活细胞分选纯化的NG2+/CNP-EGFP+或NG2+/β-肌动蛋白增强型黄色荧光蛋白阳性（EYFP+）祖细胞移植到出生后早期的LV后，表现出广泛的向吻侧和尾侧迁移。RMS内的EYFP+或EGFP+移植来源细胞为DLX+/Er81+或Nkx2.2+，迁移到OB，并分化为中间神经元和少突胶质细胞。在皮质下白质（SCWM）中，移植细胞分化为少突胶质细胞或星形胶质细胞。从SVZ选择性纯化的NG2+/EYFP+祖细胞的移植表明，这些细胞具有迁移能力，并在OB、海马体和纹状体中生成神经胶质细胞和神经元。相比之下，皮质、OB或小脑的NG2+细胞迁移潜力非常有限，仅在SCWM和纹状体中生成神经胶质细胞。我们的研究结果表明NG2+祖细胞存在区域特异性差异，并表明NG2+细胞可以在整个RMS中迁移，并在出生后的OB中促进神经胶质生成和神经发生。
