Figure 6. Radial patterning in arterial diversity and disease.
A–D, Transverse sections of the left anterior descending coronary artery and the left pulmonary and left common carotid arteries (CCA) and aorta at ~E17, stained for SMA (red), EC marker (VE-cadherin in A and PECAM in B–D; white) and DAPI (nuclei, blue). Walls range from one to five smooth muscle layers thick. E, Differences in the radial signal gradient (see Fig. 5B) could determine the thickness of specific developing arteries. F–J, Sections through the developing left CCA (panel C) at the embryonic ages indicated and stained with SMA (red), PECAM (white) and DAPI (nuclei, blue). (Panels F-H are longitudinal sections of the third aortic arch artery, which later becomes the CCA, and panels I, J are transverse sections of the CCA.) Note the gradual increase in SMA+ cell layers from rare first layer cells at E10.5 to four continuous circumferentially elongated layers at E16.5. K, L, Fate mapping of CCA first layer SMC marker+ cells in SMMHC-CreERT2, Rosa26RmTmG/+ embryos induced with a single low dose of tamoxifen (0.5mg) at E10.25. First layer CCA SMCs give rise to outer layer SMCs (marked by *), as for the PA (Figs. 4D, E, S4). Despite the different sizes and origins of the vascular wall cells (PA from mesenchyme, see Figs. 1F, J, S1C; CCA from neural crest, see ((Jiang et al., 2000; Le Lievre and Le Douarin, 1975)), radial invasion occurs in both vessels. M, N, Transverse sections of descending aortic walls stained for SMA, PECAM and nuclei (DAPI) in control(panel M, SM22-Cre) and a conditional PDGFR-β gain-of-function mutation activated specifically in smooth muscle (panel N, PDGFR-β(+/J), SM22-Cre indicated by PDGFR-β*). (The PDGFR-βJ allele, a V536A mutation that disrupts an inhibitory juxtamembrane region and results in constitutive PDGFR-β activity, isa knock-in at the endogenous PDGFR-β locus (Olson and Soriano, 2011)). Note that the mutant wall has more than twice the normal number of smooth muscle layers but the normal number of elastic layers (i, e, o) (N; Olson and Soriano, 2011), whereas in the PA there was no observable phenotype (see Fig. S5D). O, Changes in the radial signaling gradient may contribute to diseases characterized by vessel wall thickening or thinning. E, endothelial layer; 1–9, smooth muscle layers 1–9; Lu, vessel lumen; i, internal elastic lamina; e, elastic lamina; o, external elastic lamina. Scale bars, 10 μm.