論文 - 詳細
| RRC ID | 48856 |
|---|---|
| 著者 | Xiang J, Bandura J, Zhang P, Jin Y, Reuter H, Edgar BA. |
| タイトル | EGFR-dependent TOR-independent endocycles support Drosophila gut epithelial regeneration. |
| ジャーナル | Nat Commun |
| Abstract |
Following gut epithelial damage, epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signalling triggers Drosophila intestinal stem cells to produce enteroblasts (EBs) and enterocytes (ECs) that regenerate the gut. As EBs differentiate into ECs, they become postmitotic, but undergo extensive growth and DNA endoreplication. Here we report that EGFR/RAS/MAPK signalling is required and sufficient to drive damage-induced EB/EC growth. Endoreplication occurs exclusively in EBs and newborn ECs that inherit EGFR and active MAPK from fast-dividing progenitors. Mature ECs lack EGF receptors and are refractory to growth signalling. Genetic tests indicated that stress-dependent EGFR/MAPK promotes gut regeneration via a novel mechanism that operates independently of Insulin/Pi3K/TOR signalling, which is nevertheless required in nonstressed conditions. The E2f1 transcription factor is required for and sufficient to drive EC endoreplication, and Ras/Raf signalling upregulates E2f1 levels posttranscriptionally. We illustrate how distinct signalling mechanisms direct stress-dependent versus homeostatic regeneration, and highlight the importance of postmitotic cell growth in gut epithelial repair. |
| 巻・号 | 8 |
| ページ | 15125 |
| 公開日 | 2017-5-9 |
| DOI | 10.1038/ncomms15125 |
| PII | ncomms15125 |
| PMID | 28485389 |
| PMC | PMC5436070 |
| MeSH | Animals Cell Differentiation Cell Proliferation Clone Cells Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Endoreduplication Enterocytes / metabolism Enterocytes / pathology Epithelial Cells / metabolism Epithelial Cells / pathology Epithelium / physiology* ErbB Receptors / metabolism* Homeostasis Intestines / cytology* Mitogen-Activated Protein Kinases / metabolism Models, Biological Ploidies Receptors, Invertebrate Peptide / metabolism* Regeneration* Signal Transduction TOR Serine-Threonine Kinases / metabolism* Transcription, Genetic Up-Regulation / genetics ras Proteins / metabolism |
| IF | 12.121 |
| 引用数 | 31 |
| 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 | 14 |
| 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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