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Young lymphatic cells vacate their parent vein


Young lymphatic cells vacate their parent vein

Kaska Koltowska, Anne Lagendijk and colleagues from the Hogan lab and Francois lab have just published their discovery that Vegfc drives assymetric cell division of precursor cells and Prox1 upregulation to generate lymphatic cells. Published in the prestigious journal Cell Reports, the discovery was chosen for the December cover.


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



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.

Koltowska K*, Lagendijk AK*, Pichol-Thievend C, Fischer JC, Francois M, Ober EA, Yap AS, Hogan BM. Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish. Cell Reports 2015 Dec 1; 13(9): 1828–1841. *Co-first authors. Cover art


About the cover
Lymphatic vessels derive from pre-existing veins of the developing embryo. Koltowska et al. applied live imaging in zebrafish to observe cellular dynamics as one vascular lineage derives from another. They found that lymphatic precursors are bi-potential, giving rise to venous and lymphatic endothelial cells. This image captures a lymphatic cell emerging from the cardinal vein with the tip invested in the trunk midline but the base still connected to the vein.

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