Abstract:
:The formation and guidance of specialized endothelial tip cells is essential for both developmental and pathological angiogenesis. Notch-1 signalling regulates the generation of tip cells, which respond to gradients of vascular endothelial growth factor (VEGF-A). The molecular cues and signalling pathways that control the guidance of tip cells are poorly understood. Bidirectional signalling by Eph receptors and ephrin ligands represents one of the most important guidance cues involved in axon path finding. Here we show that ephrin-B2 reverse signalling involving PDZ interactions regulates endothelial tip cell guidance to control angiogenic sprouting and branching in physiological and pathological angiogenesis. In vivo, ephrin-B2 PDZ-signalling-deficient mice (ephrin-B2DeltaV) exhibit a reduced number of tip cells with fewer filopodial extensions at the vascular front in the mouse retina. In pathological settings, impaired PDZ signalling decreases tumour vascularization and growth. Mechanistically, we show that ephrin-B2 controls VEGF receptor (VEGFR)-2 internalization and signalling. Importantly, internalization of VEGFR2 is necessary for activation and downstream signalling of the receptor and is required for VEGF-induced tip cell filopodial extension. Together, our results suggest that ephrin-B2 at the tip cell filopodia regulates the proper spatial activation of VEGFR2 endocytosis and signalling to direct filopodial extension. Blocking ephrin-B2 reverse signalling may be an attractive alternative or combinatorial anti-angiogenic therapy strategy to disrupt VEGFR2 function in tumour angiogenesis.
journal_name
Naturejournal_title
Natureauthors
Sawamiphak S,Seidel S,Essmann CL,Wilkinson GA,Pitulescu ME,Acker T,Acker-Palmer Adoi
10.1038/nature08995subject
Has Abstractpub_date
2010-05-27 00:00:00pages
487-91issue
7297eissn
0028-0836issn
1476-4687pii
nature08995journal_volume
465pub_type
杂志文章相关文献
NATURE文献大全abstract::Knowledge of the composition of the Earth's core is important for understanding its melting point and therefore the temperature at the inner-core boundary and the temperature profile of the core and mantle. In addition, the partitioning of light elements between solid and liquid, as the outer core freezes at the inner...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35012056
更新日期:2000-05-11 00:00:00
abstract::The CD4 subset of cells displays helper/inducer activity and recognizes class II antigens of the major histocompatibility complex (MHC), while the CD8 subset recognizes class I MHC antigens and exhibits cytotoxic or suppressor function. Considerable functional as well as corresponding phenotypic heterogeneity exists w...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/330479a0
更新日期:1987-12-03 00:00:00
abstract::As the extracellular matrix at the original site of a neuromuscular junction seems to play a major part in the specificity of synaptic regeneration, considerable attention has been paid to unique molecules localized to this region. Here we describe an extracellular matrix glycoprotein of the elasmobranch electric orga...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/314441a0
更新日期:1985-04-04 00:00:00
abstract::Asexual reproduction by free-living invertebrate larvae is a rare and enigmatic phenomenon and, although it is known to occur in sea stars and brittle stars, it has not been detected in other echinoderms despite more than a century of intensive study. Here we describe spontaneous larval cloning in three species from t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/425146a
更新日期:2003-09-11 00:00:00
abstract::The process of DNA recognition by the activated form of the restriction endonuclease from E. coli K involves three enzyme-DNA complexes which can be differentiated experimentally. These are: an initial complex formed at a nonspecific site; a recognition complex involving the host specificity site; and a cleavage compl...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/256556a0
更新日期:1975-08-14 00:00:00
abstract::The spacing of opening-mode fractures in layered materials--such as certain sedimentary rocks and laminated engineering materials--is often proportional to the thickness of the fractured layer. Experimental studies of this phenomenon show that the spacing initially decreases as extensional strain increases in the dire...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35001550
更新日期:2000-02-17 00:00:00
abstract::The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13072
更新日期:2014-04-24 00:00:00
abstract::Growth factors raise intracellular pH (pHi) by stimulating Na+/H+ exchange in the absence of HCO3-. In mutant cells that lack the Na+/H+ exchange activity, this alkalinization does not occur, and the cells do not proliferate without artificial elevation of pHi. It has therefore been widely suggested that an early pHi ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/337648a0
更新日期:1989-02-16 00:00:00
abstract::Immune-challenged vertebrate females transfer specific antibodies to their offspring, but this gratuitous immunity cannot operate in invertebrates. Here we show that constitutive immune defence is enhanced in sexual offspring of the bumble-bee Bombus terrestris L. when the parental colony is immune-challenged. Our fin...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35107138
更新日期:2001-11-29 00:00:00
abstract::Topological states of matter are characterized by topological invariants, which are physical quantities whose values are quantized and do not depend on the details of the system (such as its shape, size and impurities). Of these quantities, the easiest to probe is the electrical Hall conductance, and fractional values...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-018-0184-1
更新日期:2018-07-01 00:00:00
abstract::Information--be it classical or quantum--is measured by the amount of communication needed to convey it. In the classical case, if the receiver has some prior information about the messages being conveyed, less communication is needed. Here we explore the concept of prior quantum information: given an unknown quantum ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03909
更新日期:2005-08-04 00:00:00
abstract::Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of respon...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25501
更新日期:2018-02-22 00:00:00
abstract::In the course of synaptic transmission in the brain and periphery, acetylcholine receptors (AChRs) rapidly transduce a chemical signal into an electrical impulse. The speed of transduction is facilitated by rapid ACh association and dissociation, suggesting a binding site relatively non-selective for small cations. Se...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07923
更新日期:2009-05-21 00:00:00
abstract::Alzheimer's disease is the world's most common dementing illness. Deposition of amyloid-β peptide drives cerebral neuroinflammation by activating microglia. Indeed, amyloid-β activation of the NLRP3 inflammasome in microglia is fundamental for interleukin-1β maturation and subsequent inflammatory events. However, it r...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11729
更新日期:2013-01-31 00:00:00
abstract::Insulin is the primary hormone involved in glucose homeostasis, and impairment of insulin action and/or secretion has a critical role in the pathogenesis of diabetes mellitus. Type-II SH2-domain-containing inositol 5-phosphatase, or 'SHIP2', is a member of the inositol polyphosphate 5-phosphatase family. In vitro stud...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35051094
更新日期:2001-01-04 00:00:00
abstract::Outbreaks of haemorrhagic fever caused by the Ebola virus are associated with high mortality rates that are a distinguishing feature of this human pathogen. The highest lethality is associated with the Zaire subtype, one of four strains identified to date. Its rapid progression allows little opportunity to develop nat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35046108
更新日期:2000-11-30 00:00:00
abstract::The TE1 family of transposable elements (TEs) of Drosophila consists of unusually large transposons, cytologically visible in larval polytene chromosomes as one or more bands. They are composite elements, as their termini consist of foldback (FB) sequences which are themselves transposable. The location of FB elements...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/316081a0
更新日期:1985-07-04 00:00:00
abstract::The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteom...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11413
更新日期:2012-10-04 00:00:00
abstract::Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated androgen receptor (AR) signalling. Despite the success of recently approved therapies targeting AR signalling, such as abi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13229
更新日期:2014-06-12 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,新闻
doi:10.1038/d41586-018-05909-0
更新日期:2018-10-01 00:00:00
abstract::Growing populations and agricultural intensification have led to raised riverine nitrogen (N) loads, widespread oxygen depletion in coastal zones (coastal hypoxia)1 and increases in the incidence of algal blooms.Although recent work has suggested that individual wetlands have the potential to improve water quality2-9,...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-03042-5
更新日期:2020-12-01 00:00:00
abstract::The bacterial CRISPR/Cas9 system allows sequence-specific gene editing in many organisms and holds promise as a tool to generate models of human diseases, for example, in human pluripotent stem cells. CRISPR/Cas9 introduces targeted double-stranded breaks (DSBs) with high efficiency, which are typically repaired by no...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature17664
更新日期:2016-05-05 00:00:00
abstract::The vomeronasal organ (VNO) is a chemoreceptive organ that is thought to transduce pheromones into electrical responses that regulate sexual, hormonal and reproductive function in mammals. The characteristics of pheromone signal detection by vomeronasal neurons remain unclear. Here we use a mouse VNO slice preparation...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35015572
更新日期:2000-06-15 00:00:00
abstract::A hemispheric dichotomy on Mars is marked by the sharp contrast between the sparsely cratered northern lowland plains and the heavily cratered southern highlands. Mechanisms proposed to remove ancient crust or form younger lowland crust include one or more giant impacts, subcrustal transport by mantle convection, the ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05356
更新日期:2006-12-14 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-020-2789-4
更新日期:2020-10-01 00:00:00
abstract::Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-1 persists in a stable latent reservoir, primarily in resting memory CD4(+) T cells. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed an...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14053
更新日期:2015-01-15 00:00:00
abstract::Lyman-alpha emitters are thought to be young, low-mass galaxies with ages of approximately 10(8) yr (refs 1, 2). An overdensity of them in one region of the sky (the SSA 22 field) traces out a filamentary structure in the early Universe at a redshift of z approximately 3.1 (equivalent to 15 per cent of the age of the ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07947
更新日期:2009-05-07 00:00:00
abstract::The Late Devonian genus Ichthyostega was for many decades the earliest known tetrapod, and the sole representative of a transitional form between a fish and a land vertebrate. However, despite being known since 1932 (ref. 1) from a large collection of specimens, its morphology remained enigmatic and not what was expec...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01904
更新日期:2003-09-04 00:00:00
abstract::The promoter for a weakly expressed constitutive gene, the lactose repressor gene (lacI), has been sequenced, along with an 'up' promoter mutation Iq. The 10-fold enhancement in I expression found in Iq is the result of a single base change at position -35. To facilitate the sequencing, the lacI gene was cloned in a s...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/274762a0
更新日期:1978-08-24 00:00:00
abstract::The metabolic basis of the autosomal recessive disease cystic fibrosis (CF) remains unidentified. Elevated levels of a serum protein in CF homozygotes and obligate heterozygotes have been described. As heterozygotes are clinically unaffected, any consistently observed abnormality in these individuals is a likely point...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/326614a0
更新日期:1987-04-09 00:00:00