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
  • Sequence Analysis, RNA
  • Luminescent Proteins
  • beta Catenin/metabolism*
  • Humans
  • Veins/cytology
  • Veins/embryology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Animals
  • COUP Transcription Factor II/metabolism
  • Bone Morphogenetic Proteins/metabolism
  • Zebrafish Proteins/metabolism
  • DNA, Complementary/genetics
  • Morpholinos/genetics
  • Microscopy, Fluorescence
  • Zebrafish
  • In Situ Nick-End Labeling
  • Real-Time Polymerase Chain Reaction
  • Angiogenic Proteins/metabolism
  • Endothelial Cells/physiology*
  • Endothelial Cells/ultrastructure
  • Animals, Genetically Modified
  • HEK293 Cells
  • Gene Expression Regulation, Developmental/physiology*
  • Luciferases
(all 24)
PubMed
25564648 Full text @ Development
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
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
aggf1MO1-aggf1MRPHLNO
aggf1MO2-aggf1MRPHLNO
nr2f2MO1-nr2f2MRPHLNO
nr2f2MO2-nr2f2MRPHLNO
tp53MO4-tp53MRPHLNO
1 - 5 of 5
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Fish
Antibodies
No data available
Orthology
No data available
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
EosEFGEos
GAL4EFGGAL4
GAL4FFEFGGAL4FF
GFPEFGGFP
mCherryEFGmCherry
RFPEFGRFP
1 - 7 of 7
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Mapping
No data available