ZFIN ID: ZDB-PUB-150809-5
mafba is a downstream transcriptional effector of Vegfc signaling essential for embryonic lymphangiogenesis in zebrafish
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.
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
Microarrays: 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.
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.