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UQ Centre for Cardiac and Vascular Biology Publications


 

mafba a critical regulator of zebrafish lymphangiogenesis

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mafba a critical regulator of zebrafish lymphangiogenesis

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.

Koltowska K, Paterson S, Bower NI, Baillie GJ, Lagendijk AK, Astin JW, Chen H, Francois M, Crosier PS, Taft RJ, Simons C, Smith KA, Hogan BM. mafba is a downstream transcriptional effector of Vegfc signaling essential for embryonic lymphangiogenesis in zebrafish. Genes & Development 2015 Aug 1;29(15):1618-30.

© 2015 Koltowska et al.; Published by Cold Spring Harbor Laboratory Press.

Koltowska Genes & Development 2015 cover

 




About the cover:

mafba
is essential for the normal formation of the lymphatic vascular network in zebrafish. Shown here is a live-image lateral view of facial and brain vasculature in a 5-d-old transgenic zebrafish expressing EGFP (pseudocolored yellow) under the control of the endothelial cell-specific promoter fli1a as well as DsRed (psuedocolored blue) under the control of the lymphatic vessel-specific promoter lyve1. The overlay of endothelial nuclei and lymphatic vessels (white) allows the accurate quantification of total lymphatic endothelial cell numbers during normal embryonic development. mafba mutants display aberrant medial and branchial arch lymphatic vasculature in the face.