V2a and V2b neurons are generated by the final divisions of pair-producing progenitors in the zebrafish spinal cord
V2a and V2b neurons are generated by the final divisions of pair-producing progenitors in the zebrafish spinal cord
复制标题
DOI：
10.1242/dev.024802
复制
发表时间：
2008-09-15
期刊：
影响因子：
4.6
通讯作者：
Higashijima, Shin-ichi
中科院分区：
文献类型：
--
作者：
Kimura, Yukiko;Satou, Chie;Higashijima, Shin-ichi
腹侧脊髓中的p2前体结构域产生两种中间神经元亚型：V2a和V2b。Delta-Notch介导的有丝分裂后未成熟神经元之间的细胞-细胞相互作用与神经元亚型的分离有关。然而，V2a和V2b神经元之间的谱系关系尚未见报道。我们使用TG[vsx1：gfp]斑马鱼来解决这个问题，这是一个模型系统，在这个系统中，高GFP表达是在p2祖细胞的最后阶段附近启动的。用延时显微镜观察子代的细胞命运。结果表明，绝大多数(如果不是全部)GFP标记的p2前体细胞一次分裂产生V2a/V2b神经元对，表明V2a和V2b神经元是由产生对的前体细胞的不对称分裂产生的。结合Notch信号参与细胞命运指定过程的证据，我们的结果强烈表明姐妹细胞之间的Delta-Notch相互作用在这些不对称分裂的最终结果中发挥着关键作用。这种决定细胞命运的机制类似于果蝇神经发生期间发生的不对称分裂，在果蝇神经发生过程中，神经节母细胞分裂一次，产生不同的神经元。然而，与果蝇不同的是，斑马鱼p2祖细胞的分裂轴并不是固定的。我们报告说，在脊椎动物的神经发生中，产生配对的祖细胞的末端分裂可以通过一种可能不依赖于分裂轴方向的机制重复地产生两个不同的神经元。
The p2 progenitor domain in the ventral spinal cord gives rise to two interneuron subtypes: V2a and V2b. Delta-Notch-mediated cell-cell interactions between postmitotic immature neurons have been implicated in the segregation of neuron subtypes. However, lineage relationships between V2a and V2b neurons have not been reported. We address this issue using Tg[vsx1:GFP] zebrafish, a model system in which high GFP expression is initiated near the final stage of p2 progenitors. Cell fates were followed in progeny using time-lapse microscopy. Results indicate that the vast majority, if not all, of GFP-labeled p2 progenitors divide once to produce V2a/V2b neuron pairs, indicating that V2a and V2b neurons are generated by the asymmetric division of pair-producing progenitor cells. Together with evidence that Notch signaling is involved in the cell fate specification process, our results strongly suggest that Delta-Notch interactions between sister cells play a crucial role in the final outcome of these asymmetric divisions. This mechanism for determining cell fate is similar to asymmetric divisions that occur during Drosophila neurogenesis, where ganglion mother cells divide once to produce distinct neurons. However, unlike in Drosophila, the divisional axes of p2 progenitors in zebrafish were not fixed. We report that the terminal division of pair-producing progenitor cells in vertebrate neurogenesis can reproducibly produce two distinct neurons through a mechanism that may not depend on the orientation of the division axis.