Fig. 8. Schematic models for nerve-mediated arterial differentiation and vascular branching in the limb skin. (A) Proposed sequence of events in vascularization of limb. A low concentration of VEGFA, or a distinct nerve-derived signal (`factor X') promotes nerve-vessel alignment, followed by VEGFA/NP-1-dependent arteriogenesis in nerve-aligned vessels. Modified from Cleaver and Krieg (Cleaver and Krieg, 1999). (B) VEGF promotes arteriogenesis via an NRP1-mediated positive-feedback loop. All vessels (blue) are initially equivalent. Nerve-derived VEGFA promotes arterial differentiation and NRP1 amplifies the VEGFA effect due to increased sensitivity to VEGF¹⁶⁴ in vessels in close proximity to nerves (N, green). A, artery.