Junb controls lymphatic vascular development in zebrafish via miR-182
Kristin Kiesow1, Katrin Bennewitz2,3, Laura Gutierrez Miranda1
1Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
Abstract:
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.
Insights
The Junb/miR-182/Foxo1 axis is crucial for lymphatic vascular development in zebrafish. This study identifies miR-182 as a novel JUNB target, revealing its role in lymphatic morphogenesis.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- JUNB, a subunit of the AP-1 transcription factor, regulates gene expression and is involved in blood vessel development and tumor suppression.
- The role of JUNB and its downstream targets in lymphatic vascular development is not fully understood.
Purpose of the Study:
- To investigate the role of JUNB and its novel target, miR-182, in lymphatic vascular development in zebrafish.
- To elucidate the regulatory mechanisms governing lymphatic morphogenesis.
Main Methods:
- Loss-of-function studies using morpholino-mediated knockdown.
- CRISPR/Cas9 gene editing technology in zebrafish.
- Analysis of gene expression, including foxo1.
Main Results:
- Identified miR-182 as a novel target gene of JUNB.
- Demonstrated a novel function for JUNB and miR-182 in zebrafish lymphatic vascular development.
- Showed that miR-182 attenuates foxo1 expression, highlighting the importance of balanced Foxo1 levels.
Conclusions:
- The Junb/miR-182/Foxo1 regulatory axis is a key player in lymphatic vascular morphogenesis in zebrafish.
- This axis represents a novel mechanism controlling lymphatic development.
