Figure 4.

Stages of lymphangiogenesis. Lymphatic endothelial cells (LECs) are derived from venous endothelial precursors during development. The expression of lymphatic-specific receptors, like VEGFR-3, allows for LEC to migrate and separate from veins in response to chemotactic guidance cues. Following the establishment of lymphatic sacs, a cohort of growth factors drives the proliferation and remodeling of the early lymphatic plexus from mid-gestation through the early postnatal period. The maturation of large collecting lymphatic vessels, which include valves and lymphatic smooth muscle cells, also occurs during the late gestation and postnatal periods. AM, adrenomedulin; CLR/Ramp2, calcitonin-like receptor/receptor activity modifying protein-2.