title: mafba is a downstream transcriptional effector of Vegfc signaling essential for embryonic lymphangiogenesis in zebrafish.
abstract: The lymphatic vasculature plays roles in tissue fluid balance, immune cell trafficking, fatty acid absorption, cancer metastasis, and cardiovascular disease. Lymphatic vessels form by lymphangiogenesis, the sprouting of new lymphatics from pre-existing vessels, in both development and disease contexts. The apical signaling pathway in lymphangiogenesis is the VEGFC/VEGFR3 pathway, yet how signaling controls cellular transcriptional output remains unknown. We used a forward genetic screen in zebrafish to identify the transcription factor mafba as essential for lymphatic vessel development. We found that mafba is required for the migration of lymphatic precursors after their initial sprouting from the posterior cardinal vein. mafba expression is enriched in sprouts emerging from veins, and we show that mafba functions cell-autonomously during lymphatic vessel development. Mechanistically, Vegfc signaling increases mafba expression to control downstream transcription, and this regulatory relationship is dependent on the activity of SoxF transcription factors, which are essential for mafba expression in venous endothelium. Here we identify an indispensable Vegfc-SoxF-Mafba pathway in lymphatic development.
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Koltowska
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Scott
authors.initials: S
authors.lastname: Paterson
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Neil I
authors.initials: NI
authors.lastname: Bower
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Baillie
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Anne K
authors.initials: AK
authors.lastname: Lagendijk
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Astin
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Huijun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Mathias
authors.initials: M
authors.lastname: Francois
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Crosier
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Cas
authors.initials: C
authors.lastname: Simons
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Smith
authors.affiliation: Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Hogan
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D042583:Lymphangiogenesis / Q000235:genetics*; D042601:Lymphatic Vessels / Q000196:embryology*; D051258:MafB Transcription Factor / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051258:MafB Transcription Factor; D009419:Nerve Tissue Proteins; D042582:Vascular Endothelial Growth Factor C; D029961:Zebrafish Proteins; C111092:mafb protein, zebrafish; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Mafb; Sox18; Sox7; Vegfc; lymphatic; vascular; zebrafish