期刊
JOURNAL OF CELL BIOLOGY
卷 217, 期 9, 页码 3285-3300出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201711167
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资金
- Austrian Federal Ministry of Education, Science and Research
- Austrian Academy of Sciences
- Austrian Science Fund [Z_153_B09]
- City of Vienna
- European Research Council under the European Union's Horizon 2020 research and innovation programme [695642, 693184]
- European Research Council under the FP7 programme [250342]
- Boehringer Ingelheim Fonds PhD fellowship
- European Molecular Biology Organization Long-Term Fellowship [LTF 1280-2014]
- European Research Council (ERC) [250342, 695642, 693184] Funding Source: European Research Council (ERC)
Drosophila melanogaster neural stem cells (neuroblasts [NBs]) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Although the machinery for asymmetric protein segregation is well understood, the events that reprogram one of the two daughter cells toward terminal differentiation are less clear. In this study, we use time-resolved transcriptional profiling to identify the earliest transcriptional differences between the daughter cells on their way toward distinct fates. By screening for coregulated protein complexes, we identify vacuolar-type H+-ATPase (v-ATPase) among the first and most significantly down-regulated complexes in differentiating daughter cells. We show that v-ATPase is essential for NB growth and persistent activity of the Notch signaling pathway. Our data suggest that v-ATPase and Notch form a regulatory loop that acts in multiple stem cell lineages both during nervous system development and in the adult gut. We provide a unique resource for investigating neural stem cell biology and demonstrate that cell fate changes can be induced by transcriptional regulation of basic, cell-essential pathways.
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