title: Junb controls lymphatic vascular development in zebrafish via miR-182.
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.
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Kiesow
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, D-68167, Germany.|Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Bennewitz
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Laura Gutierrez
authors.initials: LG
authors.lastname: Miranda
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, D-68167, Germany.|Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Stoll
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartenstein
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
authors.affiliation: Department of Vascular Biology and Tumor Angiogenesis, Center for Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Heidelberg University, Mannheim, D-68167, Germany.|Division of Vascular Oncology and Metastasis, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Kroll
authors.affiliation: Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Schorpp-Kistner
mesh_terms: D000818:Animals; D000066630:Ectopic Gene Expression; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D042583:Lymphangiogenesis; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D013897:Thoracic Duct / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun; D029961:Zebrafish Proteins; C576354:foxo1a protein, zebrafish