Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse

Development of a vascular system involves the assembly of two principal cel l types - endothelial cells and vascular smooth muscle cells/pericytes (vSM C/PC) - into many different types of blood vessels. Most, if not all, vesse ls begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitm ent of pericytes to brain capillaries and to the kidney glomerular capillar y tuft. Here, we used desmin and alpha-smooth muscle actin (ASMA) as marker s to analyze vSMC/PC development in PDGF-B-/- and PDGFR beta(-/-) 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-beta-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-beta(-/-) embryos, limb arterial vSMC showed a reduced BrdU-labeli ng index. This suggests a role of PDGF-B in vSMC/PC cell proliferation duri ng vascular growth. Two modes of vSMC recruitment to newly formed vessels h ave previously been suggested: (1) de nova formation of vSMC by induction o f undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexistimg pool of VSMC, Our data support both modes of vSMC/P C development and lead to a model in which PDGFR-beta-positive vSMC/PC prog enitors initially form around certain vessels by PDGF-B-independent inducti on. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B- dependent vSMC/PC progenitor comigration and proliferation, and/or PDGF-B-i ndependent new induction of vSMC/PC, depending on tissue context.