Tmem2 regulates embryonic Vegf signaling by controlling hyaluronic acid turnover

De Angelis, Jessica E., Lagendijk, Anne K., Chen, Huijun, Tromp, Alisha, Bower, Neil I., Tunny, Kathryn A., Brooks, Andrew J., Bakkers, Jeroen, Francois, Mathias, Yap, Alpha S., Simons, Cas, Wicking, Carol, Hogan, Benjamin M. and Smith, Kelly A. (2017) Tmem2 regulates embryonic Vegf signaling by controlling hyaluronic acid turnover. Developmental Cell, 40 2: 123-136. doi:10.1016/j.devcel.2016.12.017

Author De Angelis, Jessica E.
Lagendijk, Anne K.
Chen, Huijun
Tromp, Alisha
Bower, Neil I.
Tunny, Kathryn A.
Brooks, Andrew J.
Bakkers, Jeroen
Francois, Mathias
Yap, Alpha S.
Simons, Cas
Wicking, Carol
Hogan, Benjamin M.
Smith, Kelly A.
Title Tmem2 regulates embryonic Vegf signaling by controlling hyaluronic acid turnover
Journal name Developmental Cell   Check publisher's open access policy
ISSN 1878-1551
Publication date 2017-01-23
Sub-type Article (original research)
DOI 10.1016/j.devcel.2016.12.017
Open Access Status Not yet assessed
Volume 40
Issue 2
Start page 123
End page 136
Total pages 14
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
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.
Keyword Angiogenesis
Extracellular matrix
Hyaluronic acid
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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