Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone

Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone
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DOI:
10.1523/jneurosci.3572-04.2004
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发表时间:
2004-11-17
影响因子:
5.3
通讯作者:
Gallo, V
Gallo, V
中科院分区:
医学1区
文献类型:
--
作者:
Aguirre, A;Gallo, V

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我们使用2 ',3'-环核苷酸3 '-磷酸二酯酶(CNP)增强的绿色荧光蛋白(EGFP)转基因小鼠研究出生后脑室下区(SVZ)祖细胞的命运,重点是嗅球(OB)。CNP-EGFP小鼠出生后的OB含有EGFP(+)中间神经元和少突胶质细胞。在前SVZ中,大多数EGFP(+)祖细胞为NG 2(+)。这些NG 2(+)/EGFP(+)祖细胞表达OB中间神经元标记Er 81、成神经细胞标记doublecortin(DC)和Distalless-related homeobox(DLX)或少突胶质细胞祖细胞标记Nkx2.2。在吻侧迁移流(RMS)中,EGFP(+)细胞显示迁移表型。这些细胞的一部分是NG 2(-)/Er 81(+)/DC+/DLX+或NG 2(+)/Nkx2.2(+)。将DiI(1,1 '-双十八烷基-3,3,3',3 '-四甲基吲哚羰花青高氯酸盐)注射到出生后早期小鼠的侧脑室(LV)中,证实NG 2(+)/EGFP(+)祖细胞从SVZ通过RMS迁移到OB。此外,移植到出生后早期LV中的荧光激活细胞分选纯化的NG 2(+)/CNP-EGFP(+)或NG 2(+)/β-肌动蛋白增强的黄色荧光蛋白阳性(EYFP+)祖细胞显示出广泛的吻侧和尾侧迁移。RMS内EYFP+或EGFP(+)移植物来源的细胞为DLX+/Er 81(+)或Nkx2.2(+),迁移至OB,并分化为中间神经元和少突胶质细胞。在皮质下白色物质(SCWM)中,移植细胞分化为少突胶质细胞或星形胶质细胞。移植从SVZ选择性纯化的NG 2(+)/EYFP+祖细胞显示这些细胞是迁移的,并在OB、海马和纹状体中产生胶质细胞和神经元。相反,皮质、OB或小脑NG 2(+)细胞的迁移能力非常有限,并在SCWM和纹状体中产生胶质细胞。我们的研究结果表明NG 2(+)祖细胞之间存在区域特异性差异,并表明NG 2(+)细胞可以在整个RMS中迁移,并有助于出生后OB中的胶质细胞和神经发生。
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.