Defective blood vessel development and pericyte/pvSMC distribution in alpha 4 integrin-deficient mouse embryos |
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Authors: | Grazioli Alison Alves Christina S Konstantopoulos Konstantinos Yang Joy T |
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Institution: | Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. |
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Abstract: | 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. |
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Keywords: | Blood vessel development Cell motility α4β1 integrin Fibronectin Pericyte Presumptive vascular smooth muscle cell |
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