Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression

作者：Guoxin Feng, Peishan Yi, Yihong Yang, Yongping Chai, Dong Tian, Zhiwen Zhu, Jianhong Liu, Fanli Zhou, Ze Cheng, Xiangming Wang, Wei Li, Guangshuo Ou · 发表于：Development · 年份：2013 · DOI：10.1242/dev.098723 · 被引用次数：53 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Plant Molecular Biology Research、Pluripotent Stem Cells Research

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.