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Cover The C-terminal PDZ interaction site of ephrinB2 is required for normal development of lymphatic vasculature. Shown here is an immunofluorescence analysis of wild-type mouse ear skin, using antibodies directed against -smooth muscle actin (red) and the lymphatic endothelial markers podoplanin (blue) and LYVE-1 (green). Lymphatic capillaries transfer fluid from peripheral tissues to collecting vessels, which return the lymph fluid to the cardiovascular system. While podoplanin (blue) is expressed both in the lymphatic capillaries and collecting vessels, LYVE-1 (green) is predominantly expressed in the lymphatic capillaries, which are devoid of -SMA-positive smooth muscle cells. Mice lacking the ephrinB2 PDZ interaction site fail to remodel their primary lymphatic vascular network into a functional hierarchical vasculature and establish the capillary versus collecting lymphatic vessel identity. (For details, see Mkinen et al., p. 397.)

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