Skip to main content
. 2023 Jan 14;12(2):319. doi: 10.3390/cells12020319

Figure 1.

Figure 1

Guidance mechanisms for lymphatic network patterning in different stages of lymphatic vessel development. (A) Preexisting lymphatic vessels align with nearby blood vessels by reacting to guidance molecules released by arteries and smooth muscle cells. Guidance at this stage is mediated by the molecules VEGF-C and CXCL12 and the receptors VEGFR-3, CXCR4, CXCR7, CALCRL, and RAMP2. (A’) Vascular endothelial growth factor (VEGF)-C binds to surface proteins on the lymphatic endothelial cell (LEC) matrix and is processed into mature VEGF-C. VEGF-C processing is primarily mediated by CCBE1 and ADAMTS13. (B) VEGF-C binding to VEGF receptor (VEGFR)-2/3 and interaction with integrins induces LEC proliferation; α5 and β1 integrins also play a role at this step. (C) Macrophages release additional guidance molecules that initiate lymphatic vessel sprouting and branching. VEGF-C binding to its receptor VEGFR-3 and the coreceptor NRP2 drives this step, along with β1 integrins. (D) Deflection of lymphatic vessels during network formation occurs via release of repulsive guidance cues such as SEMA3G from nearby blood vessels. VEGFR-3, NRP2, and PLXN1 form a receptor complex that binds VEGF-C [18]. Reproduced with permission.