論文 - 詳細
| RRC ID | 87587 |
|---|---|
| 著者 | Lin J, Deng Q, Gao Y, Tan YS, Zhong Z, Tan LKA, Tan BOP, Virshup DM, Bosch JA, Perrimon N, Wang H. |
| タイトル | Microproteins Simba1 and Simba2 activate Wingless signaling during the reactivation of neural stem cells in Drosophila. |
| ジャーナル | Nat Commun |
| Abstract |
The ability of neural stem cells (NSCs) to switch between quiescent and proliferative states is fundamental for adult neurogenesis and regeneration. Microproteins or short open reading frame (sORF)-encoded peptides (SEPs), are highly abundant yet largely understudied, and their role in brain development remains unclear. Here, we demonstrate that two evolutionarily-conserved microprotein paralogs, Simba1 and Simba2, encoded by sORFs CG15715 and CG18081, respectively, govern the reactivation of Drosophila quiescent NSCs. Both Simba1 and Simba2 function in NSCs and Blood-Brain-Barrier (BBB) glial cells to promote NSC reactivation. Mechanistically, Simba1 and Simba2 act as transcription factors activating the WNT/Wingless signalling pathway during NSC reactivation. We uncover a critical role of Wg signalling molecules in promoting NSC reactivation and the translocation of Wingless from BBB glia to NSCs. Our findings reveal a role for microproteins Simba1/2 in regulating NSC reactivation through Wg signalling. Moreover, our bioinformatic analysis and luciferase assay suggest that ZNF706, the human ortholog of Simba1/2, is required for WNT signaling activation in human cells. The conserved function of Simba1/2/ZNF706 in activating WNT/Wg signalling in Drosophila and humans suggests that this new regulatory paradigm may be applicable to broader cellular processes and disease conditions. |
| 巻・号 | 16(1) |
| ページ | 11651 |
| 公開日 | 2025-11-26 |
| DOI | 10.1038/s41467-025-66727-3 |
| PII | 10.1038/s41467-025-66727-3 |
| PMID | 41298547 |
| PMC | PMC12749969 |
| MeSH | Animals Drosophila Drosophila Proteins* / genetics Drosophila Proteins* / metabolism Drosophila melanogaster* / genetics Drosophila melanogaster* / metabolism Humans Micropeptides Neural Stem Cells* / cytology Neural Stem Cells* / metabolism Neurogenesis Neuroglia / metabolism Signal Transduction Transcription Factors* / genetics Transcription Factors* / metabolism Wnt Signaling Pathway* Wnt1 Protein* / genetics Wnt1 Protein* / metabolism |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | DGRC#112853 DGRC#105188 |