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 e...

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Bibliographic Details
Published in:Developmental biology 2006-05, Vol.293 (1), p.165-177
Main Authors: Grazioli, Alison, Alves, Christina S, Konstantopoulos, Konstantinos, Yang, Joy T
Format: Article
Language:English
Subjects:
Animals
Cell Movement - physiology
Cells, Cultured
Embryo, Mammalian
Fibronectins - biosynthesis
Fibronectins - genetics
Integrin alpha4 - genetics
Integrin alpha4 - physiology
Integrin alpha4beta1 - biosynthesis
Integrin alpha4beta1 - genetics
Integrin alpha4beta1 - physiology
Integrin beta1 - physiology
Mice
Myocytes, Smooth Muscle - physiology
Neovascularization, Pathologic - embryology
Neovascularization, Pathologic - genetics
Pericytes - metabolism
Pericytes - physiology
Vascular Cell Adhesion Molecule-1 - biosynthesis
Vascular Cell Adhesion Molecule-1 - genetics
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Summary: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.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2006.01.026