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.
All data generated or analysed during this study are included in the manuscript and supporting files.
- Benjamin M Hogan
- Benjamin M Hogan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All zebrafish work was conducted in accordance with the guidelines of the animal ethic committee guidelines at the University of Queensland and of the National Cerebral and Cardiovascular Center (No.14005 and No.15010).
- Holger Gerhardt, Max Delbrück Centre for Molecular Medicine, Germany
© 2019, Grimm et al.
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