Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development
Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development
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DOI：
10.1523/jneurosci.0778-05.2005
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发表时间：
2005-07-13
影响因子：
5.3
通讯作者：
Huttner, WB
中科院分区：
文献类型：
--
作者：
Calegari, F;Haubensak, W;Huttner, WB
在哺乳动物大脑的胚胎发育过程中，已知心室区祖细胞的平均细胞周期长度增加。然而，对于任何给定的皮层发育区域和神经发生阶段，细胞周期的长度被认为在两个共存的祖细胞亚群中是相似的[即，那些经历（对称）增殖分裂和那些经历（不对称或对称）神经元生成分裂]。利用累积溴脱氧尿苷标记tis21 -绿色荧光蛋白敲入小鼠胚胎，这两个祖细胞亚群可以在体内区分，我们现在表明，在端脑神经发生的开始和晚期，经历神经元生成分裂的祖细胞的细胞周期明显长于经历增殖分裂的祖细胞。此外，我们发现最近发现的在脑室区基底侧和脑室下区分裂的神经元祖细胞比在脑室表面分裂的神经元祖细胞具有更长的G(2)期。这些发现与假设（Calegari和Huttner， 2003）一致，即细胞周期延长可以导致神经祖细胞从增殖性分裂转向神经元生成分裂，并且可能对一般的体细胞干细胞的扩增具有重要意义。
During embryonic development of the mammalian brain, the average cell-cycle length of progenitor cells in the ventricular zone is known to increase. However, for any given region of the developing cortex and stage of neurogenesis, the length of the cell cycle is thought to be similar in the two coexisting subpopulations of progenitors [i.e., those undergoing ( symmetric) proliferative divisions and those undergoing ( either asymmetric or symmetric) neuron-generating divisions]. Using cumulative bromodeoxyuridine labeling of Tis21-green fluorescent protein knock-in mouse embryos, in which these two subpopulations of progenitors can be distinguished in vivo, we now show that at the onset as well as advanced stages of telencephalic neurogenesis, progenitors undergoing neuron-generating divisions are characterized by a significantly longer cell cycle than progenitors undergoing proliferative divisions. In addition, we find that the recently characterized neuronal progenitors dividing at the basal side of the ventricular zone and in the subventricular zone have a longer G(2) phase than those dividing at the ventricular surface. These findings are consistent with the hypothesis (Calegari and Huttner, 2003) that cell-cycle lengthening can causally contribute to neural progenitors switching from proliferative to neuron-generating divisions and may have important implications for the expansion of somatic stem cells in general.