Dubreuil V, Hirsch M R, Pattyn A, Brunet J F, Goridis C
Laboratoire de Génétique et Physiologie du Développement, IBDM, CNRS-INSERM-Université de la Méditerranée-AP de Marseille, Campus de Luminy case 907, France.
Development. 2000 Dec;127(23):5191-201. doi: 10.1242/dev.127.23.5191.
In the vertebrate neural tube, cell cycle exit of neuronal progenitors is accompanied by the expression of transcription factors that define their generic and sub-type specific properties, but how the regulation of cell cycle withdrawal intersects with that of cell fate determination is poorly understood. Here we show by both loss- and gain-of-function experiments that the neuronal-subtype-specific homeodomain transcription factor Phox2b drives progenitor cells to become post-mitotic. In the absence of Phox2b, post-mitotic neuronal precursors are not generated in proper numbers. Conversely, forced expression of Phox2b in the embryonic chick spinal cord drives ventricular zone progenitors to become post-mitotic neurons and to relocate to the mantle layer. In the neurons thus generated, ectopic expression of Phox2b is sufficient to initiate a programme of motor neuronal differentiation characterised by expression of Islet1 and of the cholinergic transmitter phenotype, in line with our previous results showing that Phox2b is an essential determinant of cranial motor neurons. These results suggest that Phox2b coordinates quantitative and qualitative aspects of neurogenesis, thus ensuring that neurons of the correct phenotype are generated in proper numbers at the appropriate times and locations.
在脊椎动物的神经管中，神经祖细胞退出细胞周期伴随着转录因子的表达，这些转录因子决定了它们的一般特性和亚型特异性特性，但细胞周期退出的调控与细胞命运决定的调控如何相互作用却知之甚少。在这里，我们通过功能丧失和功能获得实验表明，神经元亚型特异性同源结构域转录因子Phox2b驱动祖细胞进入有丝分裂后状态。在没有Phox2b的情况下，有丝分裂后神经元前体的产生数量不正常。相反，在胚胎鸡脊髓中强制表达Phox2b会驱使脑室区祖细胞成为有丝分裂后神经元并迁移到套层。在这样产生的神经元中，Phox2b的异位表达足以启动一个运动神经元分化程序，其特征是表达Islet1和胆碱能递质表型，这与我们之前的结果一致，即Phox2b是颅运动神经元的一个重要决定因素。这些结果表明，Phox2b协调神经发生的数量和质量方面，从而确保在适当的时间和位置产生正确表型的神经元，且数量合适。
