Extracellular bone morphogenetic protein modulator BMPER and twisted gastrulation homolog 1 preserve arterial-venous specification in zebrafish blood vessel development and regulate Notch signaling in endothelial cells

The FEBS Journal
Jennifer Susanne EsserMartin Moser

Abstract

The bone morphogenetic protein (BMP) signaling pathway plays a central role during vasculature development. Mutations or dysregulation of the BMP pathway members have been linked to arteriovenous malformations. In the present study, we investigated the effect of the BMP modulators bone morphogenetic protein endothelial precursor-derived regulator (BMPER) and twisted gastrulation protein homolog 1 (TWSG1) on arteriovenous specification during zebrafish development and analyzed downstream Notch signaling pathway in human endothelial cells. Silencing of bmper and twsg1b in zebrafish embryos by morpholinos resulted in a pronounced enhancement of venous ephrinB4a marker expression and concomitant dysregulated arterial ephrinb2a marker expression detected by in situ hybridization. As arteriovenous specification was disturbed, we assessed the impact of BMPER and TWSG1 protein stimulation on the Notch signaling pathway on endothelial cells from different origin. Quantitative real-time PCR (qRT-PCR) and western blot analysis showed increased expression of Notch target gene hairy and enhancer of split, HEY1/2 and EPHRINB2. Consistently, silencing of BMPER in endothelial cells by siRNAs decreased Notch signaling and downstream effectors. ...Continue Reading

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Citations

Aug 27, 2019·F1000Research·Jennifer Fang, Karen Hirschi
Mar 2, 2021·Frontiers in Cell and Developmental Biology·Ting XieChanggeng Xu
Apr 13, 2021·Angiogenesis·Corina MarzianoKaren K Hirschi
Jun 8, 2021·Journal of Lipid and Atherosclerosis·Hiroyuki NakajimaNaoki Mochizuki
Jul 3, 2021·International Journal of Molecular Sciences·Ljuba C PonomarevAn Zwijsen

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