Phospholipase Cγ2 is necessary for separation of blood and lymphatic vasculature in mice

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 C gamma 2 (PLC gamma 2), by positional candidate cloning. The blood-lymph shunt observed in PLC gamma 2-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 PLC gamma 2-null bone marrow cells. These findings indicate that PLC gamma 2 plays an essential role in initiating and maintaining the separation of the blood and lymphatic vasculature.