Migration from a mitogenic niche promotes cell-cycle exit
Migration from a mitogenic niche promotes cell-cycle exit
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DOI：
10.1523/jneurosci.1559-05.2005
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发表时间：
2005-11-09
影响因子：
5.3
通讯作者：
Segal, RA
中科院分区：
文献类型：
--
作者：
Choi, Y;Borghesani, PR;Segal, RA
在发育过程中，神经前体在一个位置增殖并迁移到其成熟功能的住所。从增殖阶段到迁移阶段的过渡是一个关键的时刻;在这个过程中的错误可能会导致肿瘤形成，精神发育迟滞或癫痫。这种转变可能是一个简单的顺序过程的结果，其中前体退出细胞周期，然后开始迁移或动态调节的过程中，迁移远离有丝分裂小生境诱导前体退出细胞周期。在这里，我们表明，使用在体内和体外的方法，颗粒细胞前体增殖时，他们暴露于外部颗粒细胞层（EGL）的微环境和退出细胞周期的结果，迁移离开这个环境。在体内，由于迁移受损而留在EGL中的颗粒细胞前体继续在EGL的促有丝分裂小生境中增殖。在体外，颗粒细胞前体细胞被引入到一个器官型小脑切片增殖优先在EGL。我们确定Sonic Hedgehog作为EGL促有丝分裂生态位的关键组成部分。总之，这些数据表明，迁移远离有丝分裂生态位促进从增殖过渡到非增殖，迁移阶段。
During development, neural precursors proliferate in one location and migrate to the residence of their mature function. The transition from a proliferative stage to a migratory stage is a critical juncture; errors in this process may result in tumor formation, mental retardation, or epilepsy. This transition could be the result of a simple sequential process in which precursors exit the cell cycle and then begin to migrate or a dynamically regulated process in which migration away from a mitogenic niche induces precursors to exit the cell cycle. Here, we show, using in vivo and in vitro approaches, that granule cell precursors proliferate when they are exposed to the microenvironment of the external granule cell layer (EGL) and exit the cell cycle as a result of migrating away from this environment. In vivo, granule cell precursors that remain in the EGL because of impaired migration continue to proliferate in the mitogenic niche of the EGL. In vitro, granule cell precursors that are introduced into an organotypic cerebellar slice proliferate preferentially in the EGL. We identify Sonic Hedgehog as a critical component of the EGL mitogenic niche. Together, these data indicate that migration away from a mitogenic niche promotes transition from a proliferative to a nonproliferative, migratory stage.