Figure 1

Molecular pathways in Lymphangiogenesis. The four-step model for lymphatic vasculature formation is summarized in this scheme. Time line of endothelial cell gene expression in lymphangiogenesis refers to the murine lymphatic system. LEC competence is the autonomous ability of venous endothelial cells to respond to an inductive signal. LEC bias is the bias toward LEC determination and is characteristic of LEC precursors; LEC bias is eventually lost in other venous endothelial cells. LEC specification is characterized by initiation of LEC budding; LEC specification occurs when biased endothelial cells differentiate. LEC differentiation is characterized by four different events, as shown in the figure. During this period lymphatic vessel differentiate and maturation occurs in a stepwise manner leading to the syntesis of all of the main lymphatic vessel components to mature lymphatics. LEC: lymphatic endothelial cell. Timing: E means embryonic days. Lyve1: lymphatic vessel endothelial hyaluronan receptor 1. Vegfr3: vascular endothelial growth-factor receptor 3. Prox1: prospero related homeobox 1. Nrp2: neuropilin 2. Tie2: endothelial cell-specific receptor. Ang1 and 2: angiopoietin 1 and 2. SLC: secondary lymphoid chemokine. D6: β-chemokine receptor. ELK3: ETS-domain protein (SRF accessory protein 2). FOXC2: forkhead box C2.