Kiesow, K., Bennewitz, K., Miranda, L.G., Stoll, S.J., Hartenstein, B., Angel, P., Kroll, J., Schorpp-Kistner, M. (2015) Junb controls lymphatic vascular development in zebrafish via miR-182. Scientific Reports. 5:15007.
JUNB, a subunit of the AP-1 transcription factor complex, mediates gene regulation in response to a plethora of extracellular stimuli. Previously, JUNB was shown to act as a critical positive regulator of blood vessel development and homeostasis as well as a negative regulator of proliferation, inflammation and tumour growth. Here, we demonstrate that the oncogenic miR-182 is a novel JUNB target. Loss-of-function studies by morpholino-mediated knockdown and the CRISPR/Cas9 technology identify a novel function for both JUNB and its target miR-182 in lymphatic vascular development in zebrafish. Furthermore, we show that miR-182 attenuates foxo1 expression indicating that strictly balanced Foxo1 levels are required for proper lymphatic vascular development in zebrafish. In conclusion, our findings uncover with the Junb/miR-182/Foxo1 regulatory axis a novel key player in governing lymphatic vascular morphogenesis in zebrafish.
