論文 - 詳細
| RRC ID | 21860 |
|---|---|
| 著者 | Lu W, Casanueva MO, Mahowald AP, Kato M, Lauterbach D, Ferguson EL. |
| タイトル | Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. |
| ジャーナル | PLoS Biol |
| Abstract |
BACKGROUND:Drosophila female germline stem cells (GSCs) reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP) ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away from the niche and differentiates. However, given that the BMP signal can be diffusible, it remains unclear how a local extracellular asymmetry is sufficient to result in a robust pattern of asymmetric division. METHODS AND FINDINGS:Here we show that GSCs are polarized with respect to the cellular niche. We first use a modified biosensor to demonstrate that the small GTPase Rac is asymmetrically activated within the GSC at the niche-GSC interface. Experiments using loss-of-function and gain-of-function mutations in Rac indicate that asymmetric Rac activity both localizes the microtubule binding protein Apc2 to orient one GSC centrosome at the niche-GSC interface during interphase and activates the Jun N-terminal kinase pathway to increase the ability of the GSC to respond to BMP ligands. Other processes act in concert with each function of Rac. Specifically, we demonstrate that the GSC cell cycle arrests at prometaphase if centrosomes are misoriented. CONCLUSIONS:Thus, the GSCs, an adult stem cell present in a cellular niche, have a niche-associated polarity that couples control of the division plane with increased response to an extracellular maintenance signal. Other processes work in parallel with the Rac-mediated polarity to ensure a robust pattern of asymmetric division. We suggest that all adult stem cells likely employ multiple, independently acting mechanisms to ensure asymmetric division to maintain tissue homeostasis. |
| 巻・号 | 10(7) |
| ページ | e1001357 |
| 公開日 | 2012-7-3 |
| DOI | 10.1371/journal.pbio.1001357 |
| PII | PBIOLOGY-D-11-05055 |
| PMID | 22802725 |
| PMC | PMC3389017 |
| MeSH | Adherens Junctions / metabolism Animals Body Patterning Cell Cycle Checkpoints Cell Differentiation Cell Nucleus / genetics Cell Nucleus / metabolism Cell Polarity Centrosome / metabolism Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / metabolism Enzyme Activation Female Germ Cells / cytology* Germ Cells / metabolism Interphase Ligands MAP Kinase Signaling System Male Ovary / cytology Ovary / metabolism Stem Cell Niche* Stem Cells / cytology Stem Cells / metabolism Testis / cytology Testis / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism* |
| IF | 7.076 |
| 引用数 | 48 |
| WOS 分野 | BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | |