論文 - 詳細
| RRC ID | 59171 |
|---|---|
| 著者 | Hu DJ, Jasper H. |
| タイトル | Control of Intestinal Cell Fate by Dynamic Mitotic Spindle Repositioning Influences Epithelial Homeostasis and Longevity. |
| ジャーナル | Cell Rep |
| Abstract |
Tissue homeostasis depends on precise yet plastic regulation of stem cell daughter fates. During growth, Drosophila intestinal stem cells (ISCs) adjust fates by switching from asymmetric to symmetric lineages to scale the size of the ISC population. Using a combination of long-term live imaging, lineage tracing, and genetic perturbations, we demonstrate that this switch is executed through the control of mitotic spindle orientation by Jun-N-terminal kinase (JNK) signaling. JNK interacts with the WD40-repeat protein Wdr62 at the spindle and transcriptionally represses the kinesin Kif1a to promote planar spindle orientation. In stress conditions, this function becomes deleterious, resulting in overabundance of symmetric fates and contributing to the loss of tissue homeostasis in the aging animal. Restoring normal ISC spindle orientation by perturbing the JNK/Wdr62/Kif1a axis is sufficient to improve intestinal physiology and extend lifespan. Our findings reveal a critical role for the dynamic control of SC spindle orientation in epithelial maintenance. |
| 巻・号 | 28(11) |
| ページ | 2807-2823.e5 |
| 公開日 | 2019-9-10 |
| DOI | 10.1016/j.celrep.2019.08.014 |
| PII | S2211-1247(19)31047-2 |
| PMID | 31509744 |
| PMC | PMC7046008 |
| MeSH | Animals Cell Division / drug effects Cell Division / genetics Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / enzymology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Drosophila melanogaster / physiology Homeostasis / physiology Intestinal Mucosa / metabolism Intestines / cytology* Intestines / drug effects Intestines / growth & development Intestines / microbiology Kinesins / genetics Kinesins / metabolism Longevity / genetics* Longevity / physiology MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / metabolism* Membrane Proteins / genetics Membrane Proteins / metabolism Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Pectobacterium carotovorum Phosphorylation RNA Interference Signal Transduction / genetics Spindle Apparatus / drug effects Spindle Apparatus / enzymology Spindle Apparatus / metabolism* Stem Cells / cytology Stem Cells / drug effects Stem Cells / metabolism* Stem Cells / microbiology Up-Regulation |
| IF | 8.109 |
| 引用数 | 4 |
| リソース情報 | |
| ショウジョウバエ | DGRC#110626 |