Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression
Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression
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DOI：
10.1242/dev.098723
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发表时间：
2013-09-15
期刊：
影响因子：
4.6
通讯作者：
Ou, Guangshuo
中科院分区：
文献类型：
--
作者：
Feng, Guoxin;Yi, Peishan;Ou, Guangshuo
神经母细胞通过不对称的细胞分裂、细胞周期退出和分化产生具有不同功能的神经元。潜在的转录调控途径仍然难以捉摸。在这里，我们对线虫进行了遗传筛选，并确定了三个进化上保守的转录因子(TF)，这些转录因子对于Q神经母细胞系的发展是必不可少的。通过活体细胞成像和遗传分析，我们证明了鹿头Tf Ham-1在细胞不对称分裂过程中调节纺锤体定位和肌球蛋白极化，PAR-1样激酶PIG-1是Ham-1的转录调控靶。TEAD Tf EGL-44与锌指Tf EGL-46物理结合，在末端分裂后指示细胞周期退出。最后，SOX结构域TFEGL-13是建立正确的神经元命运所必需的，也是充分的。遗传分析进一步证明，Ham-1、EGL-44/EGL-46和EGL-13形成三条转录调控通路。因此，我们已经确定了在不同发育阶段发挥作用的神经母细胞因子，以确保适当的神经母细胞谱系进展，并表明它们的脊椎动物同源物可能类似地调节神经发育。
Neuroblasts generate neurons with different functions by asymmetric cell division, cell cycle exit and differentiation. The underlying transcriptional regulatory pathways remain elusive. Here, we performed genetic screens in C. elegans and identified three evolutionarily conserved transcription factors (TFs) essential for Q neuroblast lineage progression. Through live cell imaging and genetic analysis, we showed that the storkhead TF HAM-1 regulates spindle positioning and myosin polarization during asymmetric cell division and that the PAR-1-like kinase PIG-1 is a transcriptional regulatory target of HAM-1. The TEAD TF EGL-44, in a physical association with the zinc-finger TF EGL-46, instructs cell cycle exit after the terminal division. Finally, the Sox domain TF EGL-13 is necessary and sufficient to establish the correct neuronal fate. Genetic analysis further demonstrated that HAM-1, EGL-44/EGL-46 and EGL-13 form three transcriptional regulatory pathways. We have thus identified TFs that function at distinct developmental stages to ensure appropriate neuroblast lineage progression and suggest that their vertebrate homologs might similarly regulate neural development.