PUBLICATION

mafba is a downstream transcriptional effector of Vegfc signaling essential for embryonic lymphangiogenesis in zebrafish

Authors
Koltowska, K., Paterson, S., Bower, N.I., Baillie, G.J., Lagendijk, A.K., Astin, J.W., Chen, H., Francois, M., Crosier, P.S., Taft, R.J., Simons, C., Smith, K.A., Hogan, B.M.
ID
ZDB-PUB-150809-5
Date
2015
Source
Genes & Development   29: 1618-30 (Journal)
Registered Authors
Crosier, Phil, Paterson, Scott, Smith, Kelly
Keywords
Mafb, Sox18, Sox7, Vegfc, lymphatic, vascular, zebrafish
Datasets
GEO:GSE97649
MeSH Terms
  • Animals
  • Cell Movement/genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Lymphangiogenesis/genetics*
  • Lymphatic Vessels/embryology*
  • MafB Transcription Factor/genetics
  • MafB Transcription Factor/metabolism*
  • Mutation
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism*
  • Signal Transduction*
  • Vascular Endothelial Growth Factor C/metabolism*
  • Vascular Endothelial Growth Factor Receptor-3/metabolism
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
26253536 Full text @ Genes & Dev.
Abstract
The lymphatic vasculature plays roles in tissue fluid balance, immune cell trafficking, fatty acid absorption, cancer metastasis, and cardiovascular disease. Lymphatic vessels form by lymphangiogenesis, the sprouting of new lymphatics from pre-existing vessels, in both development and disease contexts. The apical signaling pathway in lymphangiogenesis is the VEGFC/VEGFR3 pathway, yet how signaling controls cellular transcriptional output remains unknown. We used a forward genetic screen in zebrafish to identify the transcription factor mafba as essential for lymphatic vessel development. We found that mafba is required for the migration of lymphatic precursors after their initial sprouting from the posterior cardinal vein. mafba expression is enriched in sprouts emerging from veins, and we show that mafba functions cell-autonomously during lymphatic vessel development. Mechanistically, Vegfc signaling increases mafba expression to control downstream transcription, and this regulatory relationship is dependent on the activity of SoxF transcription factors, which are essential for mafba expression in venous endothelium. Here we identify an indispensable Vegfc-SoxF-Mafba pathway in lymphatic development.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes