論文 - 詳細
| 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 |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
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