PUBLICATION
β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels
- Authors
- Kashiwada, T., Fukuhara, S., Terai, K., Tanaka, T., Wakayama, Y., Ando, K., Nakajima, H., Fukui, H., Yuge, S., Saito, Y., Gemma, A., Mochizuki, N.
- ID
- ZDB-PUB-150108-9
- Date
- 2015
- Source
- Development (Cambridge, England) 142(3): 497-509 (Journal)
- Registered Authors
- Fukuhara, Shigetomo, Fukui, Hajime, Mochizuki, Naoki, Nakajima, Hiroyuki
- Keywords
- β-Catenin, Venous vessel development, Bmp, Aggf1, Nr2f2, Zebrafish
- MeSH Terms
-
- Angiogenic Proteins/metabolism
- Animals
- Animals, Genetically Modified
- Bone Morphogenetic Proteins/metabolism
- COUP Transcription Factor II/metabolism
- DNA, Complementary/genetics
- Endothelial Cells/physiology*
- Endothelial Cells/ultrastructure
- Gene Expression Regulation, Developmental/physiology*
- HEK293 Cells
- Humans
- In Situ Nick-End Labeling
- Luciferases
- Luminescent Proteins
- Microscopy, Fluorescence
- Morpholinos/genetics
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Analysis, RNA
- Veins/cytology
- Veins/embryology*
- Zebrafish
- Zebrafish Proteins/metabolism
- beta Catenin/metabolism*
- PubMed
- 25564648 Full text @ Development
Citation
Kashiwada, T., Fukuhara, S., Terai, K., Tanaka, T., Wakayama, Y., Ando, K., Nakajima, H., Fukui, H., Yuge, S., Saito, Y., Gemma, A., Mochizuki, N. (2015) β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels. Development (Cambridge, England). 142(3):497-509.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping