Cell Reports
Volume 13, Issue 9, 1 December 2015, Pages 1828-1841
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Article
Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish

https://doi.org/10.1016/j.celrep.2015.10.055Get rights and content
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open access

Highlights

  • Prox1 expression initiates in the zebrafish vein before secondary angiogenesis

  • Prox1 is essential for lymphangiogenesis in zebrafish

  • Bipotential precursors divide to generate venous and lymphatic endothelial cells

  • Vegfc concomitantly drives bipotential precursor division and Prox1 expression

Summary

Lymphatic vessels arise chiefly from preexisting embryonic veins. Genetic regulators of lymphatic fate are known, but how dynamic cellular changes contribute during the acquisition of lymphatic identity is not understood. We report the visualization of zebrafish lymphatic precursor cell dynamics during fate restriction. In the cardinal vein, cellular commitment is linked with the division of bipotential Prox1-positive precursor cells, which occurs immediately prior to sprouting angiogenesis. Following precursor division, identities are established asymmetrically in daughter cells; one daughter cell becomes lymphatic and progressively upregulates Prox1, and the other downregulates Prox1 and remains in the vein. Vegfc drives cell division and Prox1 expression in lymphatic daughter cells, coupling signaling dynamics with daughter cell fate restriction and precursor division.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Co-first author