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Zebrafish lymphatics on the cover of G & D

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Zebrafish lymphatics on the cover of G & D

Kaska Koltowska and colleagues from the Hogan lab have just published their work investigating mafba in embryonic lymphangiogenesis in the prestigious journal Genes & Development, where her image was chosen for the August cover.

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. Cover art

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