Aneuploid mosaicism in the developing and adult cerebellar cortex
Aneuploid mosaicism in the developing and adult cerebellar cortex
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DOI：
10.1002/cne.21648
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发表时间：
2008-04-20
影响因子：
2.5
通讯作者：
Chun, Jerold
中科院分区：
文献类型：
--
作者：
Westra, Jurjen W.;Peterson, Suzanne E.;Chun, Jerold
哺乳动物脑的几个端脑增殖区域（包括胚胎大脑皮质和出生后脑室下区（SVZ））中的神经祖细胞（NPC）显示正常细胞中的细胞分裂“缺陷”，导致非整倍体成年后代。在这里，我们确定了发展中的小脑作为一个主要的，非端脑的脊椎动物中枢神经系统（CNS），也产生非整倍体的NPC和非有丝分裂细胞的增殖区域。中期染色体分析显示，15.3%和20.8%的有丝分裂的NPC在PO和P7分别为非整倍体。通过使用小脑NPC的免疫荧光分析，我们发现染色体分离缺陷有助于产生具有非整倍体基因组互补的细胞。非有丝分裂细胞进行了评估，荧光激活细胞分选术（FACS）加上荧光原位杂交（FISH），揭示了神经元和非神经元的非整倍体群体在成年小鼠和人类小脑。两者合计，这些结果表明，神经非整倍体的患病率包括非端脑部分的轴突，并表明非整倍体细胞的产生和维持是一个广泛的，如果不是普遍的，属性的中枢神经系统的发展和组织。
Neuroprogenitor cells (NPCs) in several telencephalic proliferative regions of the mammalian brain, including the embryonic cerebral cortex and postnatal subventricular zone (SVZ), display cell division "defects" in normal cells that result in aneuploid adult progeny. Here, we identify the developing cerebellum as a major, nontelencephalic proliferative region of the vertebrate central nervous system (CNS) that also produces aneuploid NPCs and nonmitotic cells. Mitotic NPCs assessed by metaphase chromosome analyses revealed that 15.3% and 20.8% of cerebellar NPCs are aneuploid at PO and P7, respectively. By using immunofluorescent analysis of cerebellar NPCs, we show that chromosome segregation defects contribute to the generation of cells with an aneuploid genomic complement. Nonmitotic cells were assessed by fluorescence-activated cell sorting (FACS) coupled with fluorescence in situ hybridization (FISH), which revealed neuronal and nonneuronal aneuploid populations in both the adult mouse and human cerebellum. Taken together, these results demonstrate that the prevalence of neural aneuploidy includes nontelencephalic portions of the neuraxis and suggest that the generation and maintenance of aneuploid cells is a widespread, if not universal, property of central nervous system development and organization.