Genome-wide identification of endothelial cell-enriched genes in the mouse embryo

Blood. 2012 Jul 26;120(4):914-23. doi: 10.1182/blood-2011-12-398156. Epub 2012 Apr 25.

Abstract

The early blood vessels of the embryo and yolk sac in mammals develop by aggregation of de novo-forming angioblasts into a primitive vascular plexus, which then undergoes a complex remodeling process. Angiogenesis is also important for disease progression in the adult. However, the precise molecular mechanism of vascular development remains unclear. It is therefore of great interest to determine which genes are specifically expressed in developing endothelial cells (ECs). Here, we used Flk1-deficient mouse embryos, which lack ECs, to perform a genome-wide survey for genes related to vascular development. We identified 184 genes that are highly enriched in developing ECs. The human orthologs of most of these genes were also expressed in HUVECs, and small interfering RNA knockdown experiments on 22 human orthologs showed that 6 of these genes play a role in tube formation by HUVECs. In addition, we created Arhgef15 knockout and RhoJ knockout mice by a gene-targeting method and found that Arhgef15 and RhoJ were important for neonatal retinal vascularization. Thus, the genes identified in our survey show high expression in ECs; further analysis of these genes should facilitate our understanding of the molecular mechanisms of vascular development in the mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Carcinoma, Lewis Lung / blood supply
  • Carcinoma, Lewis Lung / metabolism
  • Carcinoma, Lewis Lung / pathology
  • Cells, Cultured
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Female
  • GTP Phosphohydrolases / antagonists & inhibitors
  • GTP Phosphohydrolases / physiology
  • Gene Expression Profiling*
  • Genome*
  • Guanine Nucleotide Exchange Factors / antagonists & inhibitors
  • Guanine Nucleotide Exchange Factors / physiology
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Knockout
  • Neovascularization, Physiologic*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Retina / cytology
  • Retina / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor Receptor-2 / physiology*

Substances

  • Biomarkers
  • Guanine Nucleotide Exchange Factors
  • RNA, Messenger
  • RNA, Small Interfering
  • Rhoj protein, mouse
  • Vascular Endothelial Growth Factor Receptor-2
  • GTP Phosphohydrolases