Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development
Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development
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DOI：
10.1523/jneurosci.22-03-00876.2002
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发表时间：
2002-02-01
影响因子：
5.3
通讯作者：
Macklin, WB
中科院分区：
文献类型：
--
作者：
Mallon, BS;Shick, HE;Macklin, WB
已经开发了表达由小鼠髓鞘蛋白脂质蛋白（PLP）基因启动子驱动的增强型绿色荧光蛋白（EGFP）的转基因小鼠，以研究少突胶质细胞谱系中的细胞。转基因表达与PLP的发育表达一致，少突胶质细胞分化的所有阶段的细胞都清晰可见。分析这些动物以建立新生儿皮质中少突胶质细胞祖细胞迁移、增殖和分化的时间过程。在这些动物中，NG 2蛋白聚糖阳性的少突胶质细胞祖细胞的两个群体被确定存在于出生后的脑室下区和皮质。这两个群体通过PLP基因表达的存在或不存在来区分。因此，PLP基因表达定义了NG 2阳性细胞的亚群，从出生后的早期年龄，迁移到软脑膜表面和原位增殖。EGFP（+）/NG 2（+）细胞从出生后第1天起就存在于皮质中，并且在髓鞘形成开始之前，它们作为未分化的少突胶质细胞祖细胞保留在皮质中长达3周。这些数据可以解释为在此期间皮质中存在少突胶质细胞分化的重要抑制剂，其以区域特异性方式下调以允许髓鞘形成。另一方面，少突胶质细胞祖细胞可能在皮质中保持未分化，直到原位产生诱导分化的必要信号。
Transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the mouse myelin proteolipid protein (PLP) gene promoter have been developed to investigate cells in the oligodendrocyte lineage. Transgene expression is consistent with the developmental expression of PLP, with cells at all stages of oligodendrocyte differentiation clearly visualized. These animals were analyzed to establish the time course of oligodendrocyte progenitor migration, proliferation, and differentiation in neonatal cortex. In these animals, two populations of NG2 proteoglycan-positive oligodendrocyte progenitor cells were identified that exist in postnatal subventricular zone and cortex. These two populations are distinguished by the presence or absence of PLP gene expression. Thus, PLP gene expression defines a subpopulation of NG2-positive cells from very early postnatal ages, which migrates toward the pial surface and proliferates in situ. EGFP(+)/NG2(+) cells are present in the cortex from postnatal day 1, and they remain in the cortex as undifferentiated oligodendrocyte progenitors for up to 3 weeks before myelination begins. These data could be explained by the presence of an important inhibitor of oligodendrocyte differentiation in the cortex during this period, which is downregulated in a region-specific manner to allow myelination. On the other hand, it is possible that oligodendrocyte progenitor cells remain undifferentiated in cortex until an essential signal is produced in situ to induce differentiation.