論文 - 詳細
| RRC ID | 47322 |
|---|---|
| 著者 | Sasaki N, Kiso M, Kitagawa M, Saga Y. |
| タイトル | The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis. |
| ジャーナル | Development |
| Abstract |
The rostro-caudal polarity within a somite is primarily determined by the on/off state of Notch signaling, but the mechanism by which Notch is repressed has remained elusive. Here, we present genetic and biochemical evidence that the suppression of Notch signaling is essential for the establishment of rostro-caudal polarity within a somite and that Mesp2 acts as a novel negative regulator of the Notch signaling pathway. We generated a knock-in mouse in which a dominant-negative form of Rbpj is introduced into the Mesp2 locus. Intriguingly, this resulted in an almost complete rescue of the segmental defects in the Mesp2-null mouse. Furthermore, we demonstrate that Mesp2 potently represses Notch signaling by inducing the destabilization of mastermind-like 1, a core regulator of this pathway. Surprisingly, this function of Mesp2 is found to be independent of its function as a transcription factor. Together, these data demonstrate that Mesp2 is a novel component involved in the suppression of Notch target genes. |
| 巻・号 | 138(1) |
| ページ | 55-64 |
| 公開日 | 2011-1-1 |
| DOI | 10.1242/dev.055533 |
| PII | dev.055533 |
| PMID | 21098559 |
| MeSH | Animals Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Blotting, Western Cells, Cultured Female Gene Expression Regulation, Developmental / genetics Gene Expression Regulation, Developmental / physiology Immunohistochemistry Male Mice Mice, Knockout Mice, Mutant Strains Nuclear Proteins / genetics Nuclear Proteins / metabolism* Receptors, Notch / genetics Receptors, Notch / metabolism* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics Signal Transduction / physiology* Somites / embryology* Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 5.611 |
| 引用数 | 30 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY |
| リソース情報 | |
| 遺伝子材料 | pCMV-NICD 3xFLAG (RDB14500) |