Nonselective Sister Chromatid Segregation in Mouse Embryonic Neocortical Precursor Cells
Nonselective Sister Chromatid Segregation in Mouse Embryonic Neocortical Precursor Cells
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DOI：
10.1093/cercor/bhp043
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发表时间：
2009-07-01
期刊：
影响因子：
3.7
通讯作者：
Huttner, Wieland B.
中科院分区：
文献类型：
--
作者：
Fei, Ji-Feng;Huttner, Wieland B.
我们已经研究了在小鼠胚胎发育过程中产生新皮质神经元的前体细胞是否像不朽链假说所预测的那样，在有丝分裂时非随机地分离姐妹染色单体。使用5-溴-2-脱氧尿苷(BrdU)标记和Chase的各种方案，我们在所分析的任何胚胎阶段都无法检测到保留BrdU标记的新皮质前体细胞，即使通过连续切片分析整个大脑也是如此。对有丝分裂的神经上皮细胞和放射状胶质细胞的分析表明，BrdU标记的姐妹染色单体在两个新生子细胞中均有分离，在BrdU标记后的第一次分裂中呈现镜像对称模式，在第二次分裂中表现为非镜像对称模式。综上所述，我们的数据与胚胎新皮质前体细胞在有丝分裂时选择性地将姐妹染色单体分离到一个子细胞是不相容的，因此反对在这些细胞中存在不朽的DNA链。鉴于先前报道的成人神经干细胞中存在不朽的DNA链，我们讨论了1)皮质中的胚胎和成人神经干细胞是不同的，或者2)新皮质神经元的胚胎前体细胞中的大多数是祖细胞，而不是真正的神经干细胞。
We have investigated whether the precursor cells that give rise to the neurons of the neocortex during mouse embryonic development segregate sister chromatids nonrandomly upon mitosis, as would be predicted by the immortal strand hypothesis. Using various protocols of 5-bromo-2-deoxyuridine (BrdU) labeling and chase, we were unable to detect BrdU label-retaining neocortical precursor cells at any of the embryonic stages analyzed, even when the entire brain was analyzed by serial sectioning. Analysis of mitotic neuroepithelial and radial glial cells revealed BrdU-labeled sister chromatid segregation to both nascent daughter cells, which showed a mirror-symmetrical pattern in the first and a non-mirror-symmetrical pattern in the second division after BrdU labeling. Taken together, our data are incompatible with embryonic neocortical precursor cells segregating the sister chromatids selectively to one daughter cell upon mitosis and hence argue against the existence of immortal DNA strands in these cells. In light of the previously reported existence of immortal DNA strands in adult neural stem cells, we discuss that either 1) embryonic and adult neural stem cells in the cortex are distinct or 2) that most, if not all, of the embryonic precursor cells to neocortical neurons are progenitor cells rather than true neural stem cells.