Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth.

Abstract:

:Normal vision requires the precise control of vascular growth to maintain corneal transparency. Here we provide evidence for a unique mechanism by which the Forkhead box transcription factor FoxC1 regulates corneal vascular development. Murine Foxc1 is essential for development of the ocular anterior segment, and in humans, mutations have been identified in Axenfeld-Rieger syndrome, a disorder characterized by anterior segment dysgenesis. We show that FOXC1 mutations also lead to corneal angiogenesis, and that mice homozygous for either a global (Foxc1(-/-)) or neural crest (NC)-specific (NC-Foxc1(-/-)) null mutation display excessive growth of corneal blood and lymphatic vessels. This is associated with disorganization of the extracellular matrix and increased expression of multiple matrix metalloproteinases. Heterozygous mutants (Foxc1(+/-) and NC-Foxc1(+/-)) exhibit milder phenotypes, such as disrupted limbal vasculature. Moreover, environmental exposure to corneal injury significantly increases growth of both blood and lymphatic vessels in both Foxc1(+/-) and NC-Foxc1(+/-) mice compared with controls. Notably, this amplification of the angiogenic response is abolished by inhibition of VEGF receptor 2. Collectively, these findings identify a role for FoxC1 in inhibiting corneal angiogenesis, thereby maintaining corneal transparency by regulating VEGF signaling.

authors

Seo S,Singh HP,Lacal PM,Sasman A,Fatima A,Liu T,Schultz KM,Losordo DW,Lehmann OJ,Kume T

doi

10.1073/pnas.1109540109

subject

Has Abstract

pub_date

2012-02-07 00:00:00

pages

2015-20

issue

6

eissn

0027-8424

issn

1091-6490

pii

1109540109

journal_volume

109

pub_type

杂志文章
  • Energy transport in peptide helices.

    abstract::We investigate energy transport through an alpha-aminoisobutyric acid-based 3(10)-helix dissolved in chloroform in a combined experimental-theoretical approach. Vibrational energy is locally deposited at the N terminus of the helix by ultrafast internal conversion of a covalently attached, electronically excited, azob...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0701762104

    authors: Botan V,Backus EH,Pfister R,Moretto A,Crisma M,Toniolo C,Nguyen PH,Stock G,Hamm P

    更新日期:2007-07-31 00:00:00

  • Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness.

    abstract::Protein tyrosine phosphorylation and dephosphorylation are key regulatory events in T-cell receptor (TCR) signaling. We investigated the role of the tyrosine phosphatase SHPTP1 in TCR signaling by analysis of TCR signal transduction in motheaten (me/me) mice, which lack SHPTP1 expression. As revealed by flow cytometri...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.18.9624

    authors: Lorenz U,Ravichandran KS,Burakoff SJ,Neel BG

    更新日期:1996-09-03 00:00:00

  • Pre-steady-state DNA unwinding by bacteriophage T4 Dda helicase reveals a monomeric molecular motor.

    abstract::Helicases are molecular motor enzymes that unwind and translocate nucleic acids. One of the central questions regarding helicase activity is whether the process of coupling ATP hydrolysis to DNA unwinding requires an oligomeric form of the enzyme. We have applied a pre-steady-state kinetics approach to address this qu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.232401899

    authors: Nanduri B,Byrd AK,Eoff RL,Tackett AJ,Raney KD

    更新日期:2002-11-12 00:00:00

  • Greenhouse gas emissions from alternative futures of deforestation and agricultural management in the southern Amazon.

    abstract::The Brazilian Amazon is one of the most rapidly developing agricultural areas in the world and represents a potentially large future source of greenhouse gases from land clearing and subsequent agricultural management. In an integrated approach, we estimate the greenhouse gas dynamics of natural ecosystems and agricul...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1000780107

    authors: Galford GL,Melillo JM,Kicklighter DW,Cronin TW,Cerri CE,Mustard JF,Cerri CC

    更新日期:2010-11-16 00:00:00

  • Partial purification of an enzyme from Saccharomyces cerevisiae that cleaves Holliday junctions.

    abstract::An enzyme from Saccharomyces cerevisiae that cleaves Holliday junctions was partially purified approximately 500- to 1000-fold by DEAE-cellulose chromatography, gel filtration on Sephacryl S300, and chromatography on single-stranded DNA-cellulose. The partially purified enzyme did not have any detectable nuclease acti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.21.7247

    authors: Symington LS,Kolodner R

    更新日期:1985-11-01 00:00:00

  • Object grouping based on real-world regularities facilitates perception by reducing competitive interactions in visual cortex.

    abstract::In virtually every real-life situation humans are confronted with complex and cluttered visual environments that contain a multitude of objects. Because of the limited capacity of the visual system, objects compete for neural representation and cognitive processing resources. Previous work has shown that such attentio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1400559111

    authors: Kaiser D,Stein T,Peelen MV

    更新日期:2014-07-29 00:00:00

  • Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus.

    abstract::Signaling lymphocytic activation molecule family 3 (SLAMF3/Ly9) is a coregulatory molecule implicated in T-cell activation and differentiation. Systemic lupus erythematosus (SLE) is characterized by aberrant T-cell activation and compromised IL-2 production, leading to abnormal regulatory T-cell (Treg) development/fun...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1605081113

    authors: Comte D,Karampetsou MP,Kis-Toth K,Yoshida N,Bradley SJ,Mizui M,Kono M,Solomon JR,Kyttaris VC,Tsokos GC

    更新日期:2016-08-16 00:00:00

  • Intermediate-term earthquake prediction.

    abstract::An earthquake of magnitude M and linear source dimension L(M) is preceded within a few years by certain patterns of seismicity in the magnitude range down to about (M - 3) in an area of linear dimension about 5L-10L. Prediction algorithms based on such patterns may allow one to predict approximately 80% of strong eart...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.9.3748

    authors: Keilis-Borok VI

    更新日期:1996-04-30 00:00:00

  • Human tau becomes phosphorylated and forms filamentous deposits when overexpressed in lamprey central neurons in situ.

    abstract::Microinjection of plasmids encoding human tau (htau) protein into identified lamprey reticulospinal neurons (anterior bulbar cells, or ABCs) in situ induces chronic htau expression. htau protein is transported to both the axon and dendrites of expressing ABCs by mechanisms that require the C-terminal domain of htau pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.9.4733

    authors: Hall GF,Yao J,Lee G

    更新日期:1997-04-29 00:00:00

  • The cation radicals of free base and zinc bacteriochlorin, bacteriochlorophyll, and bacteriopheophytin.

    abstract::One-electron oxidation of zinc tetraphenylbacteriochlorin and its metal-free base yielded stable cation radicals. Electron spin resonance hyperfine splittings were assigned by selective deuterations. These results indicate that the protons of the saturated rings of the bacteriochlorins carry large spin densities, in a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.3.994

    authors: Fajer J,Borg DC,Forman A,Felton RH,Dolphin D,Vegh L

    更新日期:1974-03-01 00:00:00

  • Acuity-independent effects of visual deprivation on human visual cortex.

    abstract::Visual development depends on sensory input during an early developmental critical period. Deviation of the pointing direction of the two eyes (strabismus) or chronic optical blur (anisometropia) separately and together can disrupt the formation of normal binocular interactions and the development of spatial processin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1404361111

    authors: Hou C,Pettet MW,Norcia AM

    更新日期:2014-07-29 00:00:00

  • Label-free Raman observation of cytochrome c dynamics during apoptosis.

    abstract::We performed label-free observation of molecular dynamics in apoptotic cells by Raman microscopy. Dynamic changes in cytochrome c distribution at the Raman band of 750 cm(-1) were observed after adding an apoptosis inducer to the cells. The comparison of mitochondria fluorescence images and Raman images of cytochrome ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1107524108

    authors: Okada M,Smith NI,Palonpon AF,Endo H,Kawata S,Sodeoka M,Fujita K

    更新日期:2012-01-03 00:00:00

  • Chronic, relapsing myelitis in hamsters associated with experimental measles virus infection.

    abstract::Chronic, relapsing myelitis has been induced in golden Syrian hamsters by the intracerebral inoculation of measles virus when the animals were less than 1 day old. No acute illness was seen in animals that developed myelitis, and the onset of the myelitis was at 5 to 50 weeks after infection. In most animals the illne...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.7.4297

    authors: Carrigan DR,Johnson KP

    更新日期:1980-07-01 00:00:00

  • Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity.

    abstract::NAPVSIPQ (NAP), an active fragment of the glial-derived activity-dependent neuroprotective protein, is protective at femtomolar concentrations against a wide array of neural insults and prevents ethanol-induced fetal wastage and growth retardation in mice. NAP also antagonizes ethanol inhibition of L1-mediated cell ad...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1331636100

    authors: Wilkemeyer MF,Chen SY,Menkari CE,Brenneman DE,Sulik KK,Charness ME

    更新日期:2003-07-08 00:00:00

  • Activity-dependent neurotransmitter-receptor matching at the neuromuscular junction.

    abstract::Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0607450104

    authors: Borodinsky LN,Spitzer NC

    更新日期:2007-01-02 00:00:00

  • Cloning and expression of the delayed-rectifier IsK channel from neonatal rat heart and diethylstilbestrol-primed rat uterus.

    abstract::cDNAs encoding a delayed-rectifier-type K+ channel were cloned from both neonatal rat heart and ovariectomized, diethylstilbestrol-primed rat uterus by using the polymerase chain reaction. Both clones have nucleotide sequences identical to that encoding the rat kidney IsK channel [Takumi, T., Ohkubo, H. & Nakanishi, S...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.8.2975

    authors: Folander K,Smith JS,Antanavage J,Bennett C,Stein RB,Swanson R

    更新日期:1990-04-01 00:00:00

  • Endosome fusion induced by diphtheria toxin translocation domain.

    abstract::Endosomal cargo travels through a dynamic vesicle network en route to degradation by lysosomes or recycling through the Golgi apparatus back to the cell surface. Rab5 is a key determinant of the early endosomes by organizing effector proteins in specific subdomains and mediating early endosome fusion. We find that ear...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0711707105

    authors: Antignani A,Youle RJ

    更新日期:2008-06-10 00:00:00

  • Yeast aconitase binds and provides metabolically coupled protection to mitochondrial DNA.

    abstract::Aconitase (Aco1p) is a multifunctional protein: It is an enzyme of the tricarboxylic acid cycle. In animal cells, Aco1p also is a cytosolic protein binding to mRNAs to regulate iron metabolism. In yeast, Aco1p was identified as a component of mtDNA nucleoids. Here we show that yeast Aco1p protects mtDNA from excessive...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0703078104

    authors: Chen XJ,Wang X,Butow RA

    更新日期:2007-08-21 00:00:00

  • Identification and purification of an irreversible presynaptic neurotoxin from the venom of the spider Hololena curta.

    abstract::A search for potent toxins that inhibit neuronal calcium channels in Drosophila melanogaster has resulted in the identification of a presynaptic neurotoxin from the venom of the hunting spider Hololena curta. Using Drosophila neuromuscular junction as an assay, presynaptic inhibitory activity was purified using gel fi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.10.3506

    authors: Bowers CW,Phillips HS,Lee P,Jan YN,Jan LY

    更新日期:1987-05-01 00:00:00

  • Flexible, solid-state, ion-conducting membrane with 3D garnet nanofiber networks for lithium batteries.

    abstract::Beyond state-of-the-art lithium-ion battery (LIB) technology with metallic lithium anodes to replace conventional ion intercalation anode materials is highly desirable because of lithium's highest specific capacity (3,860 mA/g) and lowest negative electrochemical potential (∼3.040 V vs. the standard hydrogen electrode...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1600422113

    authors: Fu KK,Gong Y,Dai J,Gong A,Han X,Yao Y,Wang C,Wang Y,Chen Y,Yan C,Li Y,Wachsman ED,Hu L

    更新日期:2016-06-28 00:00:00

  • G-protein alpha o subunit: mutation of conserved cysteines identifies a subunit contact surface and alters GDP affinity.

    abstract::The reversible association of alpha and beta gamma subunits of GTP-binding proteins is important for signal transmission from a variety of cell-surface receptors to intracellular effectors. Previous work showed that 1,6-bis(maleimido)hexane, which crosslinks cysteine residues, crosslinks alpha o and alpha i-1 to beta ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.21.10295

    authors: Thomas TC,Schmidt CJ,Neer EJ

    更新日期:1993-11-01 00:00:00

  • Bves directly interacts with GEFT, and controls cell shape and movement through regulation of Rac1/Cdc42 activity.

    abstract::Bves is an integral membrane protein with no determined function and no homology to proteins outside of the Popdc family. It is widely expressed throughout development in myriad organisms. Here, we demonstrate an interaction between Bves and guanine nucleotide exchange factor T (GEFT), a GEF for Rho-family GTPases. Th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0802345105

    authors: Smith TK,Hager HA,Francis R,Kilkenny DM,Lo CW,Bader DM

    更新日期:2008-06-17 00:00:00

  • Induction of the stellate configuration in cultured iris epithelial cells by adenosine and compounds related to adenosine 3':5'-cyclic monophosphate.

    abstract::Adenosine, dibutyryl cyclic AMP, monobutyryl cyclic AMP, cyclic AMP, and 5'-AMP have a remarkable morphogenetic effect on cultured iris epithelial cells obtained from adult newt. They alter the broad undulating membrane of the cell into branching strands of cytoplasm, a configuration that has been named "stellate." Th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.8.2286

    authors: Ortiz JR,Yamada T,Hsie AW

    更新日期:1973-08-01 00:00:00

  • Micro- and nanoparticles self-assembly for virtually defect-free, adjustable monolayers.

    abstract::As chips further shrink toward smaller scales, fabrication processes based on the self-assembly of individual particles into patterns or structures are often sought. One of the most popular techniques for two-dimensional assembly (self-assembled monolayers) is based on capillary forces acting on particles placed at a ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0712392105

    authors: Aubry N,Singh P,Janjua M,Nudurupati S

    更新日期:2008-03-11 00:00:00

  • The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases.

    abstract::Homologs of the chromatin-bound yeast silent information regulator 2 (SIR2) protein are found in organisms from all biological kingdoms. SIR2 itself was originally discovered to influence mating-type control in haploid cells by locus-specific transcriptional silencing. Since then, SIR2 and its homologs have been sugge...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.110148297

    authors: Landry J,Sutton A,Tafrov ST,Heller RC,Stebbins J,Pillus L,Sternglanz R

    更新日期:2000-05-23 00:00:00

  • Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex.

    abstract::The Suppressor of Fused [Su(fu)] protein plays a conserved role in the regulation of Gli transcription factors of the hedgehog (Hh) signaling pathway that controls cell fate and tissue patterning during development. In both Drosophila and mammals, Su(fu) represses Gli-mediated transcription, but the mode of its action...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.082096999

    authors: Cheng SY,Bishop JM

    更新日期:2002-04-16 00:00:00

  • Requirement of Rac1 in the development of cardiac hypertrophy.

    abstract::The development of cardiac hypertrophy is mediated, in part, by increase in NADPH oxidase activity and myocardial oxidative stress. The Rho GTPase, Rac, regulates NADPH oxidase activity through interaction with gp91(phox) and p67(phox) (in which "phox" is phagocyte oxidase). However, it is not known which Rac isoform ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0510444103

    authors: Satoh M,Ogita H,Takeshita K,Mukai Y,Kwiatkowski DJ,Liao JK

    更新日期:2006-05-09 00:00:00

  • Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation.

    abstract::Memory CD4(+) T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like struc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1512600113

    authors: Shinoda K,Hirahara K,Iinuma T,Ichikawa T,Suzuki AS,Sugaya K,Tumes DJ,Yamamoto H,Hara T,Tani-Ichi S,Ikuta K,Okamoto Y,Nakayama T

    更新日期:2016-05-17 00:00:00

  • A novel amplicon at 8p22-23 results in overexpression of cathepsin B in esophageal adenocarcinoma.

    abstract::Cathepsin B (CTSB) is overexpressed in tumors of the lung, prostate, colon, breast, and stomach. However, evidence of primary genomic alterations in the CTSB gene during tumor initiation or progression has been lacking. We have found a novel amplicon at 8p22-23 that results in CTSB overexpression in esophageal adenoca...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.21.12410

    authors: Hughes SJ,Glover TW,Zhu XX,Kuick R,Thoraval D,Orringer MB,Beer DG,Hanash S

    更新日期:1998-10-13 00:00:00

  • Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a beta-linked self-glycolipid.

    abstract::TCR-mediated recognition of beta-linked self-glycolipids bound to CD1d is poorly understood. Here, we have characterized the TCR repertoire of a CD1d-restricted type II NKT cell subset reactive to sulfatide involved in the regulation of autoimmunity and antitumor immunity. The sulfatide/CD1d-tetramer(+) cells isolated...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1000576107

    authors: Arrenberg P,Halder R,Dai Y,Maricic I,Kumar V

    更新日期:2010-06-15 00:00:00