Yap1 promotes sprouting and proliferation of lymphatic progenitors downstream of Vegfc in the zebrafish trunk
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Date
2019
Authors
Grimm, L.
Nakajima, H.
Chaudhury, S.
Bower, N.I.
Okuda, K.S.
Cox, A.G.
Harvey, N.L.
Koltowska, K.
Mochizuki, N.
Hogan, B.M.
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Journal article
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eLife, 2019; 8(e42881):e42881-1-e42881-22
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Lin Grimm, Hiroyuki Nakajima, Smrita Chaudhury, Neil I Bower, Kazuhide S Okuda, Andrew G Cox, Natasha L Harvey, Katarzyna Koltowska, Naoki Mochizuki, Benjamin M Hogan
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Abstract
Lymphatic vascular development involves specification of lymphatic endothelial progenitors that subsequently undergo sprouting, proliferation and tissue growth to form a complex second vasculature. The Hippo pathway and effectors Yap and Taz control organ growth and regulate morphogenesis and cellular proliferation. Yap and Taz control angiogenesis but a role in lymphangiogenesis remains to be fully elucidated. Here we show that YAP displays dynamic changes in lymphatic progenitors and Yap1 is essential for lymphatic vascular development in zebrafish. Maternal and Zygotic (MZ) <i>yap1</i> mutants show normal specification of lymphatic progenitors, abnormal cellular sprouting and reduced numbers of lymphatic progenitors emerging from the cardinal vein during lymphangiogenesis. Furthermore, Yap1 is indispensable for Vegfc-induced proliferation in a transgenic model of Vegfc overexpression. Paracrine Vegfc-signalling ultimately increases nuclear YAP in lymphatic progenitors to control lymphatic development. We thus identify a role for Yap in lymphangiogenesis, acting downstream of Vegfc to promote expansion of this vascular lineage.
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Copyright 2019 Grimm et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.