期刊
DEVELOPMENT
卷 140, 期 18, 页码 3838-3847出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.098723
关键词
C. elegans; Asymmetric cell division; Neuroblast development
资金
- National Basic Research Program of China [973 Program] [2012CB966800, 2012CB945002, 2013CB945600]
- National Natural Science Foundation of China [31101002, 31100972, 31171295, 31201048, 31190063, 31201009, 31222035]
- Beijing Natural Science Foundation [5123045]
- Junior Thousand Talents Program of China
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.
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