Kawaguchi Ayano, Ogawa Masaharu, Saito Kanako, Matsuzaki Fumio, Okano Hideyuki, Miyata Takaki
Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, Wako, Saitama, Japan.
J Neurosci Res. 2004 Dec 15;78(6):784-95. doi: 10.1002/jnr.20347.
Progenitor cells that generate neuron pairs ("pair progenitor cells") are implicated in mammalian cortical development, and their division has been thought to be "symmetric." However, asymmetric growth of two sister neurons generated by the division of a pair progenitor cell would lead to more efficient generation of neuronal diversity in the cortex. To explore mechanisms by which pair progenitor cells provide neuronal diversity, we examined molecular differences between a pair of neurons generated in clonal-density culture. Time-course analysis for the acquisition of neuronal markers and the disappearance of Pax6 and Neurogenin2 (Ngn2) demonstrated that 1) these transcription factors are expressed transiently in some but not all young neurons and 2) some neuron pairs showed uneven/asymmetric expression of Pax6 (19.5%) or Ngn2 (23.8%), whereas other pairs were either symmetrically positive or negative. Asymmetric Pax6 distribution in neuron pairs was not associated with asymmetric distribution of Numb, which raises an intriguing possibility, that Pax6 asymmetry in neuron pairs is produced by an alternative mode of the cell autonomous mechanisms. Stage-dependent changes were noted in the pattern of Ngn2 retention in daughter neurons, reflecting qualitative changes in the pair progenitor population. We suggest that pair progenitor cells contribute to the generation of neuronal diversity through cell-intrinsic heterogeneity and asymmetric division.
产生神经元对的祖细胞（“对祖细胞”）与哺乳动物皮质发育有关，其分裂一直被认为是“对称的”。然而，由对祖细胞分裂产生的两个姐妹神经元的不对称生长将导致皮质中神经元多样性的更有效产生。为了探索对祖细胞提供神经元多样性的机制，我们研究了在克隆密度培养中产生的一对神经元之间的分子差异。对神经元标记物的获得以及Pax6和神经生成素2（Ngn2）消失的时间进程分析表明：1）这些转录因子在一些但不是所有年轻神经元中短暂表达；2）一些神经元对显示出Pax6（19.5%）或Ngn2（23.8%）的不均匀/不对称表达，而其他对则要么对称地呈阳性，要么对称地呈阴性。神经元对中Pax6的不对称分布与Numb的不对称分布无关，这引发了一种有趣的可能性，即神经元对中Pax6的不对称是由细胞自主机制的另一种模式产生的。在子代神经元中观察到Ngn2保留模式的阶段依赖性变化，反映了对祖细胞群体的质性变化。我们认为，对祖细胞通过细胞内在异质性和不对称分裂促进神经元多样性的产生。
