Developmental and Post-Injury Cortical Gliogenesis: A Genetic Fate-Mapping Study with Nestin-CreER Mice
Developmental and Post-Injury Cortical Gliogenesis: A Genetic Fate-Mapping Study with Nestin-CreER Mice
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DOI：
10.1002/glia.20835
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发表时间：
2009-08-01
期刊：
影响因子：
6.2
通讯作者：
Kuan, Chia-Yi
中科院分区：
文献类型：
--
作者：
Burns, Kevin A.;Murphy, Brian;Kuan, Chia-Yi
无论是在发育过程中还是在成人脑损伤后，皮质胶质生成的主要来源仍然不确定。我们之前生成了 Nestin-CreER 小鼠，用于对放射状胶质细胞 (RG) 的后代进行命运图谱，RG 是神经系统中星形胶质细胞和少突胶质细胞的来源。在这里，我们发现，如果 Nestin-CreER 小鼠与 stop-floxed EGFP 小鼠杂交并在胚胎发生后期（E16-E18）接受他莫昔芬，则它们会标记另一群神经胶质祖细胞，即围产期室下区（SVZ）成胶质细胞。定量显示，E18 他莫昔芬诱导标记的围产期 SVZ 成胶质细胞多于新生儿大脑中 RG 和过渡 RG 的组合（54% 对 22%）。延时显微镜显示 SVZ 胶质母细胞经历了复杂的变态，并且经常相互转化为过渡性 RG。令人惊讶的是，E10 剂量的 RG 祖细胞产生了星形胶质细胞，但没有少突胶质细胞，而 E18 诱导的命运图谱显示了出生后大脑中的星形胶质细胞和 NG2+ 少突胶质细胞前体。这些结果表明皮质少突胶质细胞主要源自围产期 SVZ 胶质母细胞祖细胞。此外，通过结合遗传命运图谱和 BrdU 标记，我们发现皮质星形胶质细胞在出生后不久就停止增殖。
The primary sources of cortical gliogenesis, either during development or after adult brain injury, remain uncertain. We previously generated Nestin-CreER mice to fate-map the progeny of radial glial cells (RG), a source of astrocytes and oligodendrocytes in the nervous system. Here, we show that Nestin-CreER mice label another population of glial progenitors, namely the perinatal subventricular zone (SVZ) glioblasts, if they are crossed with stop-floxed EGFP mice and receive tamoxifen in late embryogenesis (E16-E18). Quantification showed E18 tamoxifen-induction labeled more perinatal SVZ glioblasts than RG and transitional RG combined in the newborn brain (54% vs. 22%). Time-lapse microscopy showed SVZ-glioblasts underwent complex metamorphosis and often-reciprocal transformation into transitional RG. Surprisingly, the E10-dosed RG progenitors produced astrocytes, but no oligodendrocytes, whereas E18-induction fate-mapped both astrocytes and NG2+ oligodendrocyte precursors in the postnatal brain. These results suggest that cortical oligodendrocytes mostly derive from perinatal SVZ glioblast progenitors. Further, by combining genetic fate-mapping and BrdU-labeling, we showed that cortical astrocytes cease proliferation soon after birth (