ZFIN ID: ZDB-PUB-170125-2
Tmem2 Regulates Embryonic Vegf Signaling by Controlling Hyaluronic Acid Turnover
De Angelis, J.E., Lagendijk, A.K., Chen, H., Tromp, A., Bower, N.I., Tunny, K.A., Brooks, A.J., Bakkers, J., Francois, M., Yap, A.S., Simons, C., Wicking, C., Hogan, B.M., Smith, K.A.
Date: 2017
Source: Developmental Cell   40: 123-136 (Journal)
Registered Authors: Bakkers, Jeroen, Hogan, Ben M., Smith, Kelly
Keywords: VEGF, angiogenesis, extracellular matrix, hyaluronic acid, tmem2, zebrafish
MeSH Terms:
  • Animals
  • Arteries/metabolism
  • Embryo, Nonmammalian/metabolism*
  • Endothelial Cells/metabolism
  • Hyaluronic Acid/metabolism*
  • Membrane Proteins/chemistry
  • Membrane Proteins/metabolism*
  • Mutation/genetics
  • Neovascularization, Physiologic
  • Phenotype
  • Polymerization
  • Signal Transduction*
  • Torso/blood supply
  • Vascular Endothelial Growth Factor A/metabolism*
  • Veins/metabolism
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/metabolism*
PubMed: 28118600 Full text @ Dev. Cell
Angiogenesis is responsible for tissue vascularization during development, as well as in pathological contexts, including cancer and ischemia. Vascular endothelial growth factors (VEGFs) regulate angiogenesis by acting through VEGF receptors to induce endothelial cell signaling. VEGF is processed in the extracellular matrix (ECM), but the complexity of ECM control of VEGF signaling and angiogenesis remains far from understood. In a forward genetic screen, we identified angiogenesis defects in tmem2 zebrafish mutants that lack both arterial and venous Vegf/Vegfr/Erk signaling. Strikingly, tmem2 mutants display increased hyaluronic acid (HA) surrounding developing vessels. Angiogenesis in tmem2 mutants was rescued, or restored after failed sprouting, by degrading this increased HA. Furthermore, oligomerized HA or overexpression of Vegfc rescued angiogenesis in tmem2 mutants. Based on these data, and the known structure of Tmem2, we find that Tmem2 regulates HA turnover to promote normal Vegf signaling during developmental angiogenesis.