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Development of a vascular system involves the assembly of two principal cell types – endothelial cells and vascular smooth muscle cells/pericytes (vSMC/PC) – into many different types of blood vessels. Most, if not all, vessels begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitment of pericytes to brain capillaries and to the kidney glomerular capillary tuft. Here, we used desmin and α-smooth muscle actin (ASMA) as markers to analyze vSMC/PC development in PDGF-B−/− and PDGFR-β−/− embryos. Both mutants showed a site-specific reduction of desmin-positive pericytes and ASMA-positive vSMC. We found that endothelial expression of PDGF-B was restricted to immature capillary endothelial cells and to the endothelium of growing arteries. BrdU labeling showed that PDGFR-β-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-B−/− embryos, limb arterial vSMC showed a reduced BrdU-labeling index. This suggests a role of PDGF-B in vSMC/PC cell proliferation during vascular growth. Two modes of vSMC recruitment to newly formed vessels have previously been suggested: (1) de novo formation of vSMC by induction of undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexisting pool of vSMC. Our data support both modes of vSMC/PC development and lead to a model in which PDGFR-β-positive vSMC/PC progenitors initially form around certain vessels by PDGF-B-independent induction. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B-dependent vSMC/PC progenitor co-migration and proliferation, and/or PDGF-B-independent new induction of vSMC/PC, depending on tissue context.

Kidney glomerulus mesangial cells fail to develop in mice carrying targeted null mutations in the platelet-derived growth factor (PDGF)-B or PDGF-Rβ genes. We have examined the pattern of expression of these genes and smooth muscle markers during kidney development, to address the possible mechanisms underlying the mutant phenotypes. In wild-type embryos, PDGF-B was expressed in vascular endothelial cells, particularly in capillary endothelial cells in the developing glomeruli, whereas PDGF-Rβ was found in perivascular mesenchymal cells in the developing renal cortex. In the course of glomerular development, small groups of PDGF-Rβ and desmin-expressing cells collected in the ‘S’-shaped and early cup-shaped vesicles, and at later stages such cells were found in the glomerular mesangium. In PDGF-B or -Rβ null embryos, some PDGF-Rβ/desmin or desmin-positive cells, respectively, were seen in early cup-shaped vesicles, but fewer than in the wild type, and further development of the mesangium failed. In mouse chimeras composed of PDGF-Rβ +/+ and −/− cells, the Rβ−/− cells failed to populate the glomerular mesangium. Our results show that while the mesangial cell lineage is specified independently of PDGF-B/Rβ, these molecules provide critical permissive signals in mesangial cell development. We propose a model in which mesangial cells originate from PDGF-Rβ-positive progenitors surrounding the developing glomerular afferent and efferent arterioles, and are co-recruited in response to PDGF-B during angiogenic formation of the glomerular capillary tuft.