Defective blood vessel development and pericyte/pvSMC distribution in α4 integrin-deficient mouse embryos

Alison Grazioli, Christina S. Alves, Konstantinos Konstantopoulos, Joy T. Yang

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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 α4 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 α4β1 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 α4 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.

Original languageEnglish (US)
Pages (from-to)165-177
Number of pages13
JournalDevelopmental biology
Volume293
Issue number1
DOIs
StatePublished - May 1 2006

Keywords

  • Blood vessel development
  • Cell motility
  • Fibronectin
  • Pericyte
  • Presumptive vascular smooth muscle cell
  • α4β1 integrin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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