Developmental stage-dependent transcriptional regulatory pathways control neuroblast lineage progression.
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.
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Guoxin
G
Feng
Peishan
P
Yi
Yihong
Y
Yang
Yongping
Y
Chai
Dong
D
Tian
Zhiwen
Z
Zhu
Jianhong
J
Liu
Fanli
F
Zhou
Ze
Z
Cheng
Xiangming
X
Wang
Wei
W
Li
Guangshuo
G
Ou
D000818:Animals; D060049:Asymmetric Cell Division / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage / Q000235:genetics*; D002467:Cell Nucleus / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics; D017124:Conserved Sequence; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks / Q000235:genetics*; D017238:Genes, Helminth / Q000235:genetics; D008018:Life Cycle Stages / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009218:Myosins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; D009218:Myosins
Asymmetric cell division; C. elegans; Neuroblast development