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Updated: Apr 21, 2026
In Vivo Imaging and Quantitation of the Host Angiogenic Response in Zebrafish Tumor Xenografts
Published on: August 14, 2019
FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular
Ju-Hoon So1, Jun-Dae Kim2, Kyeong-Won Yoo3
1Department of Biology, Chungnam National University, Daejeon, Korea; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Objective:
It has been shown that Mindbomb (Mib), an E3 Ubiquitin ligase, is an essential modulator of Notch signaling during development. However, its effects on vascular development remain largely unknown.
Approaches And Results:
We identified a number of novel proteins that physically interact with Mib, including the Factor Inhibiting Hypoxia Inducible Factor 1 (FIH-1, also known as HIF1AN) from a yeast two hybrid screen, as previously reported. In cultured cells, FIH-1 colocalizes with Mib1, corroborating their potential interaction. In zebrafish embryos, FIH-1 appears to modulate VEGF-A signaling activity; depletion of fih-1 induces ectopic expression of vascular endothelial growth factor-a (vegfa) and leads to exuberant ectopic sprouts from intersegmental vessels (ISVs). Conversely, over-expression of fih-1 substantially attenuates the formation of ISVs, which can be rescued by concurrent over-expression of vegfa, indicating that FIH-1/HIF1AN may fine tune VEGF-A signaling.
Conclusions:
Taken together, our data suggest that FIH-1 interacts with Mib E3 Ubiquitin ligase and modulates vascular development by attenuating VEGF-A signaling activity.
