Modulation mechanisms of sympathetic innervation by different levels of Sema 3A.

(A) NPR-1 is a co-receptor of VEGFR2, which is involved in VEGF signaling; NRP-1 is also a receptor for Sema 3A, after triggered by Sema 3A, it binds to Plexin A1, forming a complex implicated in modulating sympathetic innervation. (B) When the concentration of Sema 3A is low, VEGF-NRP-1-VEGFR2 signaling is dominant, thus providing chemoattractive cues for sympathetic nerve outgrowth. (C) When Sema 3A is high expressed, it mainly triggers NPR-1-VEGFR2 signaling, producing chemorepulsive cues limiting sympathetic nerve outgrowth.