Journal Article

DKFZ-2017-02901

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Junb controls lymphatic vascular development in zebrafish via miR-182.

Kiesow, K. (First author)DKFZ* ; Bennewitz, K.DKFZ* ; Miranda, L. G.DKFZ* ; Stoll, S. J.DKFZ* ; Hartenstein, B.DKFZ* ; Angel, P.DKFZ* ; Kroll, J.DKFZ* ; Schorpp-Kistner, M. (Last author)DKFZ*

2015
Nature Publishing Group London

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Please use a persistent id in citations: doi:10.1038/srep15007

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.

Keyword(s): Forkhead Box Protein O1 ; Forkhead Transcription Factors ; FoxO1 protein, zebrafish ; MicroRNAs ; Proto-Oncogene Proteins c-jun ; Zebrafish Proteins

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Contributing Institute(s):

1. Signaltransduktion/Wachstumskontrolle (A100)
2. Vaskuläre Onkologie und Metastasierung (A190)

Research Program(s):

1. 321 - Basic Concepts (POF3-321) (POF3-321)

Appears in the scientific report 2015

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