BACKGROUND: Formation of blood vessels requires the concerted regulation of an unknown number of genes in a spatial-, time- and dosage-dependent manner. Determining genes, which drive vascular maturation is crucial for the identification of new therapeutic targets against pathological angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: [corrected] We accessed global gene regulation throughout maturation of the @entity1573 chorio-allantoic membrane (CAM), a highly vascularized tissue, using pan genomic microarrays. Seven percent of analyzed genes showed a significant change in expression (>2-fold, FDR<5%) with a peak occurring from E7 to E10, when key morphogenetic and angiogenic genes such as @entity13062 , @entity2751 , @entity26657 , @entity2032 and @entity7991 were upregulated, reflecting the state of an activated endothelium. At later stages, a general decrease in gene expression occurs, including genes encoding mitotic factors or angiogenic mediators such as @entity39368 , @entity2032 , @entity70253 . We identified putative @entity1 orthologs for 77% of significantly regulated genes and determined endothelial cell enrichment for 20% of the orthologs in silico. Vascular expression of several genes including @entity70254 , @entity36459 , @entity37927 , @entity70255 , @entity47087 , @entity70256 , @entity37158 , @entity56939 , @entity11277 and @entity15695 was demonstrated by in situ hybridization. Up to 9% of the CAM genes were also overexpressed in @entity1 organs with related functions, such as placenta and lung or the thyroid. 21-66% of CAM genes enriched in endothelial cells were deregulated in several @entity1 @entity5 types (P<.0001). Interfering with @entity70256 (encoding parvin, beta) function profoundly changed @entity1 endothelial cell shape, motility and tubulogenesis, suggesting an important role of this gene in the angiogenic process. CONCLUSIONS/SIGNIFICANCE: Our study underlines the complexity of gene regulation in a highly vascularized organ during development. We identified a restricted number of novel genes enriched in the endothelium of different species and tissues, which may play crucial roles in normal and pathological angiogenesis.

Correlating global gene regulation to angiogenesis in the developing XXXX extra-embryonic vascular system.

@entity1 :: ('9606', 'Species') :: ['human'] @entity15695 :: ('6480', 'Gene') :: ['ST6GAL1'] @entity11277 :: ('284119', 'Gene') :: ['PTRF'] @entity13062 :: ('652', 'Gene') :: ['BMP4'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity2751 :: ('6608', 'Gene') :: ['SMO'] @entity70253 :: ('4192;4609', 'Gene') :: ['MDK and MYC'] @entity26657 :: ('3200', 'Gene') :: ['HOXA3'] @entity39368 :: ('3491', 'Gene') :: ['CYR61'] @entity37158 :: ('5139', 'Gene') :: ['PDE3A'] @entity1573 :: ('9031', 'Species') :: ['chick'] @entity2032 :: ('2034', 'Gene') :: ['EPAS1'] @entity7991 :: ('2263', 'Gene') :: ['FGFR2'] @entity36459 :: ('11167', 'Gene') :: ['FSTL1'] @entity70256 :: ('29780', 'Gene') :: ['PARVB'] @entity56939 :: ('5547', 'Gene') :: ['PRCP'] @entity70254 :: ('8507', 'Gene') :: ['ENC1'] @entity70255 :: ('9079', 'Gene') :: ['LDB2'] @entity47087 :: ('3987', 'Gene') :: ['LIMS1'] @entity37927 :: ('58494', 'Gene') :: ['JAM2']
@entity1573 :: (9031,Species) :: ['chick']
