Fig. 7. Model for the regulation of Vegfa expression during distal lung vascular development by FGF9 and SHH signaling. (1-3) FGF9 signaling via FGFR1 and FGFR2 stimulates SHH signaling (White et al., 2006) and Vegfa expression both in sub-mesothelial and sub-epithelial mesenchymal layers. In the absence of SHH signaling, FGF9 has a stronger affect on Vegfa expression in the sub-epithelial compartment (2) compared with the sub-mesothelial compartment (3). (4) Epithelial SHH signals to lung mesenchyme (Bellusci et al., 1997a; Weaver et al., 2003). SHH signaling is required for Vegfa expression and subsequent vascular development both in sub-mesothelial mesenchyme (5) and sub-epithelial mesenchyme (6; except for the inner-most cell layer, stippled shading). HH signaling to Flk1-Cre⁺ endothelial cells is not required for capillary development. (7) VEGF is a primary factor regulating vascular growth in the developing lung. Distal capillaries are denoted by red ovals located between sub-mesothelial and sub-epithelial mesenchyme layers.