| 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
|
| リソース情報 |
| ショウジョウバエ |
DGRC#112853
DGRC#105188 |
