| Title |
A Regulatory Transcriptional Loop Controls Proliferation and Differentiation in Drosophila Neural Stem Cells
|
|---|---|
| Published in |
PLOS ONE, May 2014
|
| DOI | 10.1371/journal.pone.0097034 |
| Pubmed ID | |
| Authors |
Tetsuo Yasugi, Anja Fischer, Yanrui Jiang, Heinrich Reichert, Juergen A. Knoblich |
| 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. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Switzerland | 1 | 2% |
| Unknown | 43 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 15 | 33% |
| Researcher | 11 | 24% |
| Student > Master | 4 | 9% |
| Student > Bachelor | 3 | 7% |
| Student > Postgraduate | 2 | 4% |
| Other | 5 | 11% |
| Unknown | 5 | 11% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 19 | 42% |
| Biochemistry, Genetics and Molecular Biology | 14 | 31% |
| Neuroscience | 3 | 7% |
| Medicine and Dentistry | 2 | 4% |
| Psychology | 1 | 2% |
| Other | 2 | 4% |
| Unknown | 4 | 9% |