論文 - 詳細
| RRC ID | 77282 |
|---|---|
| 著者 | Davis JA, Koenig AL, Lubert A, Chestnut B, Liu F, Palencia Desai S, Winkler T, Pociute K, Choi K, Sumanas S. |
| タイトル | ETS transcription factor Etsrp / Etv2 is required for lymphangiogenesis and directly regulates vegfr3 / flt4 expression. |
| ジャーナル | Dev Biol |
| Abstract |
The molecular mechanisms initiating the formation of the lymphatic system, lymphangiogenesis, are still poorly understood. Here we have identified a novel role in lymphangiogenesis for an ETS transcription factor, Etv2/Etsrp, a known regulator of embryonic vascular development. Through the use of fully validated photoactivatable morpholinos we show that inducible Etv2 inhibition in zebrafish embryos at 1 day post-fertilization (dpf) results in significant inhibition of lymphangiogenesis, while development of blood vessels is unaffected. In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including lyve1b, prox1a, and vegfr3/flt4, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein. |
| 巻・号 | 440(1) |
| ページ | 40-52 |
| 公開日 | 2018-8-1 |
| DOI | 10.1016/j.ydbio.2018.05.003 |
| PII | S0012-1606(17)30833-3 |
| PMID | 29753018 |
| PMC | PMC6054491 |
| MeSH | Animals Cell Differentiation Embryo, Nonmammalian Embryonic Stem Cells Endothelial Cells / metabolism Gene Expression Regulation, Developmental / genetics HEK293 Cells Humans Lymphangiogenesis / genetics Lymphangiogenesis / physiology* Lymphatic Vessels / embryology Lymphatic Vessels / metabolism Mice Morpholinos / metabolism Signal Transduction Transcription Factors / genetics Transcription Factors / physiology Vascular Endothelial Growth Factor C / genetics Vascular Endothelial Growth Factor Receptor-3 / genetics Zebrafish Zebrafish Proteins / genetics* Zebrafish Proteins / physiology* |
| IF | 2.896 |
| 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 | X(Twitter) |
| 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 | |
| ゼブラフィッシュ | UAS:GFP |