ZFIN ID: ZDB-PUB-190501-8
Yap1 promotes sprouting and proliferation of lymphatic progenitors downstream of Vegfc in the zebrafish trunk
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.
Lymphatic vascular development involves specification of lymphatic endothelial progenitors that subsequently undergo sprouting, proliferation and tissue growth to form a complex second vasculature. Hippo pathway and effectors Yap and Taz promote 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 Yap1 displays dynamic changes in lymphatic progenitors and is essential for lymphatic vascular development in zebrafish. Maternal and Zygotic (MZ) yap1
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 Yap1 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.