| RRC ID |
32422
|
| 著者 |
Yasugi T, Fischer A, Jiang Y, Reichert H, Knoblich JA.
|
| タイトル |
A regulatory transcriptional loop controls proliferation and differentiation in Drosophila neural stem cells.
|
| ジャーナル |
PLoS One
|
| Abstract |
Neurogenesis is initiated by a set of basic Helix-Loop-Helix (bHLH) transcription factors that specify neural progenitors and allow them to generate neurons in multiple rounds of asymmetric cell division. The Drosophila Daughterless (Da) protein and its mammalian counterparts (E12/E47) act as heterodimerization factors for proneural genes and are therefore critically required for neurogenesis. Here, we demonstrate that Da can also be an inhibitor of the neural progenitor fate whose absence leads to stem cell overproliferation and tumor formation. We explain this paradox by demonstrating that Da induces the differentiation factor Prospero (Pros) whose asymmetric segregation is essential for differentiation in one of the two daughter cells. Da co-operates with the bHLH transcription factor Asense, whereas the other proneural genes are dispensible. After mitosis, Pros terminates Asense expression in one of the two daughter cells. In da mutants, pros is not expressed, leading to the formation of lethal transplantable brain tumors. Our results define a transcriptional feedback loop that regulates the balance between self-renewal and differentiation in Drosophila optic lobe neuroblasts. They indicate that initiation of a neural differentiation program in stem cells is essential to prevent tumorigenesis.
|
| 巻・号 |
9(5)
|
| ページ |
e97034
|
| 公開日 |
2014-5-7
|
| DOI |
10.1371/journal.pone.0097034
|
| PII |
PONE-D-14-08087
|
| PMID |
24804774
|
| PMC |
PMC4013126
|
| MeSH |
Animals
Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
Basic Helix-Loop-Helix Transcription Factors / genetics
Carcinogenesis / genetics
Cell Differentiation / genetics*
Cell Proliferation / genetics
Drosophila
Drosophila Proteins / biosynthesis*
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Gene Expression Regulation, Developmental
Humans
Mitosis
Nerve Tissue Proteins / biosynthesis
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Neural Stem Cells / metabolism*
Neurogenesis / genetics
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Transcription Factors / genetics*
Transcription Factors / metabolism
Transcription, Genetic*
|
| IF |
2.74
|
| 引用数 |
4
|
|
WOS 分野
|
CELL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
|
