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PMID:10375497

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Citation

Hellström, M, Kalén, M, Lindahl, P, Abramsson, A and Betsholtz, C (1999) 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 126:3047-55

Abstract

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 alpha-smooth muscle actin (ASMA) as markers 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-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-beta-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.

Links

PubMed

Keywords

Actins/metabolism; Animals; Arteries/embryology; Arteries/metabolism; Arteries/pathology; Blood Vessels/cytology; Blood Vessels/embryology; Blood Vessels/metabolism; Brain/cytology; Brain/metabolism; Cell Division; Cell Movement; Desmin/metabolism; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Muscle, Smooth, Vascular/cytology; Muscle, Smooth, Vascular/embryology; Muscle, Smooth, Vascular/metabolism; Pericytes/cytology; Pericytes/metabolism; Platelet-Derived Growth Factor/genetics; Platelet-Derived Growth Factor/metabolism; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-sis; Receptor, Platelet-Derived Growth Factor beta; Receptors, Platelet-Derived Growth Factor/genetics; Receptors, Platelet-Derived Growth Factor/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PGFRB

involved_in

GO:0048661: positive regulation of smooth muscle cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:0048568: embryonic organ development

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:0014911: positive regulation of smooth muscle cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PGFRB

involved_in

GO:0001568: blood vessel development

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PDGFB

involved_in

GO:0048661: positive regulation of smooth muscle cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PDGFB

involved_in

GO:0014911: positive regulation of smooth muscle cell migration

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PDGFB

involved_in

GO:0001568: blood vessel development

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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