論文 - 詳細
| RRC ID | 36898 |
|---|---|
| 著者 | Shimojo H, Isomura A, Ohtsuka T, Kori H, Miyachi H, Kageyama R. |
| タイトル | Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis. |
| ジャーナル | Genes Dev |
| Abstract |
Notch signaling regulates tissue morphogenesis through cell-cell interactions. The Notch effectors Hes1 and Hes7 are expressed in an oscillatory manner and regulate developmental processes such as neurogenesis and somitogenesis, respectively. Expression of the mRNA for the mouse Notch ligand Delta-like1 (Dll1) is also oscillatory. However, the dynamics of Dll1 protein expression are controversial, and their functional significance is unknown. Here, we developed a live-imaging system and found that Dll1 protein expression oscillated in neural progenitors and presomitic mesoderm cells. Notably, when Dll1 expression was accelerated or delayed by shortening or elongating the Dll1 gene, Dll1 oscillations became severely dampened or quenched at intermediate levels, as modeled mathematically. Under this condition, Hes1 and Hes7 oscillations were also dampened. In the presomitic mesoderm, steady Dll1 expression led to severe fusion of somites and their derivatives, such as vertebrae and ribs. In the developing brain, steady Dll1 expression inhibited proliferation of neural progenitors and accelerated neurogenesis, whereas optogenetic induction of Dll1 oscillation efficiently maintained neural progenitors. These results indicate that the appropriate timing of Dll1 expression is critical for the oscillatory networks and suggest the functional significance of oscillatory cell-cell interactions in tissue morphogenesis. |
| 巻・号 | 30(1) |
| ページ | 102-16 |
| 公開日 | 2016-1-1 |
| DOI | 10.1101/gad.270785.115 |
| PII | 30/1/102 |
| PMID | 26728556 |
| PMC | PMC4701973 |
| MeSH | Animals Calcium-Binding Proteins Cell Communication Cell Proliferation Cells, Cultured Gene Expression Regulation, Developmental* Gene Knock-In Techniques Intercellular Signaling Peptides and Proteins / genetics* Intercellular Signaling Peptides and Proteins / metabolism* Mesoderm / cytology Mesoderm / embryology Mesoderm / metabolism Mice Models, Biological Morphogenesis / physiology* Mutation Neurogenesis / genetics Neurons / cytology Neurons / metabolism* Receptors, Notch / genetics Signal Transduction / genetics Somites / embryology Stem Cells / cytology Stem Cells / metabolism* Time-Lapse Imaging |
| IF | 9.527 |
| 引用数 | 62 |
| WOS 分野 | DEVELOPMENTAL BIOLOGY GENETICS & HEREDITY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | F1000Research |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| 遺伝子材料 | pDll1-Ub-Fluc (RDB14127) pDll1-Fluc (RDB14128). |