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First published online 4 December 2008
doi: 10.1242/dev.025353

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Phospholipase C2 is necessary for separation of blood and lymphatic vasculature in mice

Hirotake Ichise^1,*,, Taeko Ichise^1,*, Osamu Ohtani² and Nobuaki Yoshida¹

¹ Laboratory of Gene Expression and Regulation, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
² Department of Anatomy, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.

Author for correspondence (e-mail: h-ichise{at}ims.u-tokyo.ac.jp)

Accepted 15 November 2008

SUMMARY

The lymphatic vasculature originates from the blood vasculature through a mechanism relying on Prox1 expression and VEGFC signalling, and is separated and kept separate from the blood vasculature in a Syk- and SLP76-dependent manner. However, the mechanism by which lymphatic vessels are separated from blood vessels is not known. To gain an understanding of the vascular partitioning, we searched for the affected gene in a spontaneous mouse mutant exhibiting blood-filled lymphatic vessels, and identified a null mutation of the Plcg2 gene, which encodes phospholipase C2 (PLC2), by positional candidate cloning. The blood-lymph shunt observed in PLC2-null mice was due to aberrant separation of blood and lymphatic vessels. A similar phenotype was observed in lethally irradiated wild-type mice reconstituted with PLC2-null bone marrow cells. These findings indicate that PLC2 plays an essential role in initiating and maintaining the separation of the blood and lymphatic vasculature.

Key words: Mouse, PLC2, Lymphangiogenesis, Vascular separation, Bone marrow-derived cells, Endothelial cell

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