Koutmani Yassemi, Hurel Catherine, Patsavoudi Evangelia, Hack Michael, Gotz Magdalena, Thomaidou Dimitra, Matsas Rebecca
Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, Athens 115 21, Greece.
Eur J Neurosci. 2004 Nov;20(10):2509-23. doi: 10.1111/j.1460-9568.2004.03724.x.
Progression of progenitor cells towards neuronal differentiation is tightly linked with cell cycle control and the switch from proliferative to neuron-generating divisions. We have previously shown that the neuronal protein BM88 drives neuroblastoma cells towards exit from the cell cycle and differentiation into a neuronal phenotype in vitro. Here, we explored the role of BM88 during neuronal birth, cell cycle exit and the initiation of differentiation in vivo. By double- and triple-labelling with the S-phase marker BrdU or the late G2 and M-phase marker cyclin B1, antibodies to BM88 and markers of the neuronal or glial cell lineages, we demonstrate that in the rodent forebrain, BM88 is expressed in multipotential progenitor cells before terminal mitosis and in their neuronal progeny during the neurogenic interval, as well as in the adult. Further, we defined at E16 a cohort of proliferative progenitors that exit S phase in synchrony, and by following their fate for 24 h we show that BM88 is associated with the dynamics of neuron-generating divisions. Expression of BM88 was also evident in cycling cortical radial glial cells, which constitute the main neurogenic population in the cerebral cortex. In agreement, BM88 expression was markedly reduced and restricted to a smaller percentage of cells in the cerebral cortex of the Small eye mutant mice, which lack functional Pax6 and exhibit severe neurogenesis defects. Our data show an interesting correlation between BM88 expression and the progression of progenitor cells towards neuronal differentiation during the neurogenic interval.
祖细胞向神经元分化的进程与细胞周期调控以及从增殖性分裂向神经元生成性分裂的转变紧密相关。我们之前已经表明，神经元蛋白BM88可驱使神经母细胞瘤细胞在体外退出细胞周期并分化为神经元表型。在此，我们探究了BM88在体内神经元生成、细胞周期退出及分化起始过程中的作用。通过用S期标记物BrdU或晚G2期和M期标记物细胞周期蛋白B1、BM88抗体以及神经元或神经胶质细胞谱系标记物进行双重和三重标记，我们证明在啮齿动物前脑中，BM88在终末有丝分裂前的多能祖细胞中表达，在神经发生间期其神经元后代中表达，在成体中也表达。此外，我们在E16定义了一群同步退出S期的增殖祖细胞，并追踪它们24小时的命运，结果表明BM88与神经元生成性分裂的动态过程相关。BM88在循环的皮质放射状胶质细胞中也有明显表达，这些细胞构成了大脑皮质中的主要神经发生群体。同样，在小眼突变小鼠的大脑皮质中，BM88的表达明显降低且局限于较小比例的细胞中，这些小鼠缺乏功能性Pax6并表现出严重的神经发生缺陷。我们的数据显示了在神经发生间期BM88表达与祖细胞向神经元分化进程之间存在有趣的相关性。
