Defective blood vessel development and pericyte/pvSMC distribution in alpha 4 integrin-deficient mouse embryos.
Blood vessel development is in part regulated by pericytes/presumptive vascular smooth muscle cells (PC/pvSMCs). Here, we demonstrate that interactions between PC/pvSMCs and extracellular matrix play a critical role in this event. We show that the cranial vessels in alpha4 integrin-deficient mouse embryos at the stage of vessel remodeling are increased in diameter. This defect is accompanied by a failure of PC/pvSMCs, which normally express alpha4beta1 integrin, to spread uniformly along the vessels. We also find that fibronectin but not VCAM-1 is localized in the cranial vessels at this stage. Furthermore, cultured alpha4 integrin-null PC/pvSMCs plated on fibronectin display a delay in initiating migration, a reduction in migration speed, and a decrease in directional persistence in response to a polarized force of shear flow. These results suggest that specific motile activities of PC/pvSMCs regulated by mechanical signals imposed by the interstitial extracellular matrix may also be required in vivo for the distribution and function of the PC/pvSMCs during blood vessel development.
Grazioli
Alison
A
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Alves
Christina S
CS
Konstantopoulos
Konstantinos
K
Yang
Joy T
JT
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D039441:Integrin alpha4 / Q000235:genetics / Q000502:physiology*; D039041:Integrin alpha4beta1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019012:Integrin beta1 / Q000502:physiology*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000196:embryology* / Q000235:genetics*; D020286:Pericytes / Q000378:metabolism / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
D005353:Fibronectins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4