β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels
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- Takeru Kashiwada
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Shigetomo Fukuhara
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Kenta Terai
- Laboratory of Function and Morphology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan
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- Toru Tanaka
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Yuki Wakayama
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Koji Ando
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Hiroyuki Nakajima
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Hajime Fukui
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Shinya Yuge
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
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- Yoshinobu Saito
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
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- Akihiko Gemma
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo 113-8603, Japan
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- Naoki Mochizuki
- Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan
Description
<jats:p>β-catenin regulates the transcription of genes involved in diverse biological processes, including embryogenesis, tissue homeostasis and regeneration. Endothelial cell (EC)-specific gene-targeting analyses in mice have revealed that β-catenin is required for vascular development. However, the precise function of β-catenin-mediated gene regulation in vascular development is not well understood, since β-catenin regulates not only gene expression but also the formation of cell-cell junctions. To address this question, we have developed a novel transgenic zebrafish line that allows the visualization of β-catenin transcriptional activity specifically in ECs and discovered that β-catenin-dependent transcription is central to the bone morphogenetic protein (Bmp)-mediated formation of venous vessels. During caudal vein (CV) formation, Bmp induces the expression of aggf1, a putative causative gene for Klippel–Trenaunay syndrome, which is characterized by venous malformation and hypertrophy of bones and soft tissues. Subsequently, Aggf1 potentiates β-catenin transcriptional activity by acting as a transcriptional co-factor, suggesting that Bmp evokes β-catenin-mediated gene expression through Aggf1 expression. Bmp-mediated activation of β-catenin induces the expression of Nr2f2 (also known as Coup-TFII), a member of the nuclear receptor superfamily, to promote the differentiation of venous ECs, thereby contributing to CV formation. Furthermore, β-catenin stimulated by Bmp promotes the survival of venous ECs, but not that of arterial ECs. Collectively, these results indicate that Bmp-induced activation of β-catenin through Aggf1 regulates CV development by promoting the Nr2f2-dependent differentiation of venous ECs and their survival. This study demonstrates, for the first time, a crucial role of β-catenin-mediated gene expression in the development of venous vessels.</jats:p>
Journal
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- Development
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Development 142 497-, 2015-01-01
The Company of Biologists
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Details 詳細情報について
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- CRID
- 1360848661908244736
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- ISSN
- 14779129
- 09501991
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- Data Source
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- Crossref
- KAKEN