Abstract:
:Integrity of the blood vessel wall is essential for vascular homeostasis and organ function. A dynamic balance between endothelial cell survival and apoptosis contributes to this integrity during vascular development and pathological angiogenesis. The genetic and molecular mechanisms regulating these processes in vivo are still largely unknown. Here, we show that Birc2 (also known as cIap1) is essential for maintaining endothelial cell survival and blood vessel homeostasis during vascular development. Using a forward-genetic approach, we identified a zebrafish null mutant for birc2, which shows severe hemorrhage and vascular regression due to endothelial cell integrity defects and apoptosis. Using genetic and molecular approaches, we show that Birc2 positively regulates the formation of the TNF receptor complex I in endothelial cells, thereby promoting NF-kappaB activation and maintaining vessel integrity and stabilization. In the absence of Birc2, a caspase-8-dependent apoptotic program takes place that leads to vessel regression. Our findings identify Birc2 and TNF signaling components as critical regulators of vascular integrity and endothelial cell survival, thereby providing an additional target pathway for the control of angiogenesis and blood vessel homeostasis during embryogenesis, regeneration and tumorigenesis.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Santoro MM,Samuel T,Mitchell T,Reed JC,Stainier DYdoi
10.1038/ng.2007.8subject
Has Abstractpub_date
2007-11-01 00:00:00pages
1397-402issue
11eissn
1061-4036issn
1546-1718pii
ng.2007.8journal_volume
39pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome. Here we describe two patients with a heterozygous nonsense mutation in exon 2 o...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/91070
更新日期:2001-08-01 00:00:00
abstract::The maintenance of chromosome termini, or telomeres, requires the action of the enzyme telomerase, as conventional DNA polymerases cannot fully replicate the ends of linear molecules. Telomerase is expressed and telomere length is maintained in human germ cells and the great majority of primary human tumours. However,...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1297-498
更新日期:1997-12-01 00:00:00
abstract::Here we report an integrated analysis that leverages data from treatment of genetic mouse models of prostate cancer along with clinical data from patients to elucidate new mechanisms of castration resistance. We show that castration counteracts tumor progression in a Pten loss-driven mouse model of prostate cancer thr...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2650
更新日期:2013-07-01 00:00:00
abstract::Elucidating how and to what extent CpG islands (CGIs) are methylated in germ cells is essential to understand genomic imprinting and epigenetic reprogramming. Here we present, to our knowledge, the first integrated epigenomic analysis of mammalian oocytes, identifying over a thousand CGIs methylated in mature oocytes....
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.864
更新日期:2011-06-26 00:00:00
abstract::All molybdoenzymes other than nitrogenase require molybdopterin as a metal-binding cofactor. Several genes necessary for the synthesis of the molybdenum cofactor (MoCo) have been characterized in bacteria and plants. The proteins encoded by the Escherichia coli genes moaA and moaC catalyse the first steps in MoCo synt...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/1706
更新日期:1998-09-01 00:00:00
abstract::We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top S...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.353
更新日期:2009-05-01 00:00:00
abstract::Variation for metabolite composition and content is often observed in plants. However, it is poorly understood to what extent this variation has a genetic basis. Here, we describe the genetic analysis of natural variation in the metabolite composition in Arabidopsis thaliana. Instead of focusing on specific metabolite...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1815
更新日期:2006-07-01 00:00:00
abstract::There is increasing evidence showing that the stromal cells surrounding cancer epithelial cells, rather than being passive bystanders, might have a role in modifying tumor outgrowth. The molecular basis of this aspect of carcinoma etiology is controversial. Some studies have reported a high frequency of genetic aberra...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.117
更新日期:2008-05-01 00:00:00
abstract::Transcriptional silencing by CpG island methylation is a prevalent mechanism of tumor-suppressor gene suppression in cancers. Genetic experiments have defined the importance of the DNA methyltransferase Dnmt1 for the maintenance of methylation in mouse cells and its role in neoplasia. In human bladder cancer cells, se...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1068
更新日期:2003-01-01 00:00:00
abstract::We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atheroscleros...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1245
更新日期:2003-10-01 00:00:00
abstract::The degree to which genetic factors influence human intelligence remains a matter of some controversy. However, there is little doubt that single gene mutations can significantly alter brain development and function. For example, mutations affecting the FMR1 gene cause the fragile X syndrome, the most prevalent known ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1195-331
更新日期:1995-11-01 00:00:00
abstract::Urolithiasis is one of the most common urologic diseases in industrialized societies. Calcium oxalate is the predominant component in 70-80% of kidney stones, and small changes in urinary oxalate concentration affect the risk of stone formation. SLC26A6 is an anion exchanger expressed on the apical membrane in many ep...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1762
更新日期:2006-04-01 00:00:00
abstract::Characterization of the polycystic kidney disease 1 (PKD1) gene has been complicated by genomic rearrangements on chromosome 16. We have used an exon linking strategy, taking RNA from a cell line containing PKD1 but not the duplicate loci, to clone a cDNA contig of the entire transcript. The transcript consists of 14,...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0695-151
更新日期:1995-06-01 00:00:00
abstract::We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P<5×10(-8)), increasing the number of known susceptibility loci to 25. The most assoc...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2395
更新日期:2012-10-01 00:00:00
abstract::PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1415
更新日期:2004-10-01 00:00:00
abstract::Genetic integrity is crucial to normal cell function, and mutations in genes required for DNA replication and repair underlie various forms of genetic instability and disease, including cancer. One structural feature of intact genomes is runs of homopolymeric dC/dG. Here we describe an unusual mutator phenotype in Cae...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng928
更新日期:2002-08-01 00:00:00
abstract::The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggeste...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/6023
更新日期:1999-02-01 00:00:00
abstract::Genome-wide association studies with SNP markers are expected to allow identification of genes that underlie complex disorders. Hundreds of thousands of SNP markers will be required for comprehensive genome-wide association studies. The development of microarray-based methods for SNP genotyping on this scale remains a...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1558
更新日期:2005-06-01 00:00:00
abstract::Retinitis pigmentosa is an untreatable, inherited retinal disease that leads to blindness. The disease initiates with the loss of night vision due to rod photoreceptor degeneration, followed by irreversible, progressive loss of cone photoreceptor. Cone loss is responsible for the main visual handicap, as cones are ess...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1386
更新日期:2004-07-01 00:00:00
abstract::Mutations in PRKCSH, encoding the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1357
更新日期:2004-06-01 00:00:00
abstract::The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor. Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy-negati...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0695-224
更新日期:1995-06-01 00:00:00
abstract::The plant circadian clock is a complex network of genes crucial for plant survival. A new study finds that domestication gradually slowed down the circadian clock of tomato via selection on two major genes-one that delayed phasing of the clock with daylight, whereas the other induced a longer period. ...
journal_title:Nature genetics
pub_type: 评论,杂志文章
doi:10.1038/ng.3476
更新日期:2016-01-01 00:00:00
abstract::Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusio...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2564
更新日期:2013-04-01 00:00:00
abstract::Junctional epidermolysis bullosa (JEB) is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Characteristic ultrastructural findings in JEB are abnormalities in the hemidesmosome-anchoring filament complexes. These focal attachment struc...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0995-83
更新日期:1995-09-01 00:00:00
abstract::Translocation events are frequent in cancer and may create chimeric fusions or 'regulatory rearrangements' that drive oncogene overexpression. Here we identify super-enhancer translocations that drive overexpression of the oncogenic transcription factor MYB as a recurrent theme in adenoid cystic carcinoma (ACC). Whole...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3502
更新日期:2016-03-01 00:00:00
abstract::A high-density haplotype map recently enabled a genome-wide association study (GWAS) in a population of indica subspecies of Chinese rice landraces. Here we extend this methodology to a larger and more diverse sample of 950 worldwide rice varieties, including the Oryza sativa indica and Oryza sativa japonica subspecie...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.1018
更新日期:2011-12-04 00:00:00
abstract::The diaphragm is an essential mammalian skeletal muscle, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDHs), a common and often lethal birth defect. The diaphragm is derived from multiple embryonic sources, but how these give rise to the diaphragm is unknown, and, despite the...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3250
更新日期:2015-05-01 00:00:00
abstract::Alcohol misuse is the leading cause of cirrhosis and the second most common indication for liver transplantation in the Western world. We performed a genome-wide association study for alcohol-related cirrhosis in individuals of European descent (712 cases and 1,426 controls) with subsequent validation in two independe...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3417
更新日期:2015-12-01 00:00:00
abstract::Spinocerebellar ataxia type I (SCAI) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat on chromosome 6p. Normal alleles range from 19-36 repeats while SCA1 alleles contain 43-81 repeats. We now show that in 63% of paternal transmissions, an increase in repeat numb...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1193-254
更新日期:1993-11-01 00:00:00
abstract::Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protei...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.271
更新日期:2009-01-01 00:00:00