Abstract:
:Myocardial infarction and ischemic heart disease are the leading cause of death in the industrial world. Therapies employed for treating these diseases are aimed at promoting increased blood flow to cardiac tissue. Pharmacological induction of new coronary growth has recently been explored, however, clinical trials with known proangiogenic factors have been disappointing. To identify novel therapeutic targets, we have explored signaling pathways that govern embryonic coronary development. Using a combination of genetically engineered mice and an organ culture system, we identified novel roles for fibroblast growth factor (FGF) and Hedgehog (HH) signaling in coronary vascular development. We show that FGF signals promote coronary growth indirectly by signaling to the cardiomyoblast through redundant function of Fgfr1 and Fgfr2. Myocardial FGF signaling triggers a wave of HH activation that is essential for vascular endothelial growth factor (Vegf)-A, Vegf-B, Vegf-C, and angiopoietin-2 (Ang2) expression. We demonstrate that HH is necessary for coronary vascular development and activation of HH signaling is sufficient to promote coronary growth and to rescue coronary defects due to loss of FGF signaling. These studies implicate HH signaling as an essential regulator of coronary vascular development and as a potential therapeutic target for coronary neovascularization. Consistent with this, activation of HH signaling in the adult heart leads to an increase in coronary vessel density.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Lavine KJ,White AC,Park C,Smith CS,Choi K,Long F,Hui CC,Ornitz DMdoi
10.1101/gad.1411406subject
Has Abstractpub_date
2006-06-15 00:00:00pages
1651-66issue
12eissn
0890-9369issn
1549-5477pii
20/12/1651journal_volume
20pub_type
杂志文章abstract::Covalent modifications of the histone N tails play important roles in eukaryotic gene expression. Histone acetylation, in particular, is required for the activation of a subset of eukaryotic genes through the targeted recruitment of histone acetyltransferases. We have reported that a histone C tail modification, ubiqu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1149604
更新日期:2004-01-15 00:00:00
abstract::The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily that are bound and activated by oxysterols. These receptors serve as sterol sensors to regulate the transcription of gene products that control intracellular cholesterol homeostasis through catabolism and transport. In this report, we...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.844900
更新日期:2000-11-15 00:00:00
abstract::Expression of the Arabidopsis CGS1 gene that codes for cystathionine gamma-synthase is feedback regulated at the step of mRNA stability in response to S-adenosyl-L-methionine (AdoMet). A short stretch of amino acid sequence, called the MTO1 region, encoded by the first exon of CGS1 itself is involved in this regulatio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1317105
更新日期:2005-08-01 00:00:00
abstract::Many small nucleolar RNAs (snoRNAs) in vertebrates are encoded within introns of protein genes. We have reported previously that two isoforms of human U17 snoRNA are encoded in introns of the cell-cycle regulatory gene, RCC1. We have now investigated the mechanism of processing of U17 RNAs and of another intron-encode...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.11.1411
更新日期:1995-06-01 00:00:00
abstract::Homeotic genes are expressed in spatially precise patterns during Drosophila development to control segmental differentiation. The Sex combs reduced (Scr) gene of the Antennapedia gene complex is involved in the determination of the labial and prothoracic segments of the embryo. To study both the wild-type pattern of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.716
更新日期:1987-09-01 00:00:00
abstract::Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300-CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.1.64
更新日期:1999-01-01 00:00:00
abstract::B-cell-specific transcription of immunoglobulin genes is mediated by the interaction of a POU domain containing transcription factor Oct-1 or Oct-2, with the B-cell-specific coactivator OCA-B (Bob-1, OBF-1) and a prototype octamer element. We find that OCA-B binds DNA directly in the major groove between the two subdo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.16.2079
更新日期:1996-08-15 00:00:00
abstract::Genomic imprinting is an epigenetic phenomenon leading to parentally biased gene expression. Throughout the years, extensive efforts have been made to characterize the epigenetic marks underlying imprinting in animals and plants. As a result, DNA methylation asymmetries between parental genomes emerged as the primary ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.332924.119
更新日期:2020-01-01 00:00:00
abstract::The mottler of white (mw) locus has been determined to interact with alleles of the white (w) eye color locus which are a subset of the transposable element insertion mutants. The transposable elements belong to six different types, including copia, and are located at several sites within the w gene. Three X-ray-induc...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.1.73
更新日期:1989-01-01 00:00:00
abstract::In this issue of Genes & Development, Wierzbicki and colleagues (pp. 1825-1836) examine the current model of RNA-directed DNA methylation (RdDM) by determining genome-wide distributions of RNA polymerase V (Pol V) occupancy, siRNAs, and DNA methylation. Their data support the key role of base-pairing between Pol V tra...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.200410.112
更新日期:2012-08-15 00:00:00
abstract::In Drosophila germ cells, PIWI-interacting RNAs (piRNAs) are amplified through a PIWI slicer-dependent feed-forward loop termed the ping-pong cycle, yielding secondary piRNAs. However, the detailed mechanism remains poorly understood, largely because an ex vivo model system amenable to biochemical analyses has not bee...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.283929.116
更新日期:2016-07-15 00:00:00
abstract::Integrin receptors for extracellular matrix are critical for cell motility, but the signals that determine when to stop are not known. Analysis of distal tip cell (DTC) migration during gonadogenesis in Caenorhabditis elegans has revealed the importance of transcription factor vab-3/Pax6 in regulating the alpha integr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1534807
更新日期:2007-07-01 00:00:00
abstract::Viable aristaless (al) mutations of Drosophila affect pattern elements at both ends of the proximodistal axis in a subset of adult appendages. The al gene has been cloned and identified by P-element-mediated germ-line transformation with a genomic DNA fragment, which rescues a lethal mutation of al as well as aspects ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.1.114
更新日期:1993-01-01 00:00:00
abstract::Human lymphoblastoid cells derived from different healthy individuals display considerable variation in their transcription profiles. Here we show that such variation in gene expression underlies interindividual susceptibility to DNA damaging agents. The results demonstrate the massive differences in sensitivity acros...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1688508
更新日期:2008-10-01 00:00:00
abstract::Dorsal mesoderm induction in arthropods and ventral mesoderm induction in vertebrates are closely related processes that involve signals of the BMP family. In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part, effected through the transcriptional activation and funct...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.15.2354
更新日期:1998-08-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that adds telomeric repeats to chromosomes, maintaining telomere length and stabilizing chromosome ends. In vitro, telomerase from the ciliate Tetrahymena elongates single-stranded, guanosine-rich DNA primers by adding repeats of the Tetrahymena telomeric sequence, dT2G4. We ha...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.7b.1364
更新日期:1993-07-01 00:00:00
abstract::We report a new role for Wnt signaling in the vertebrate embryo: the induction of neural tissue from ectoderm. Early expression of mouse wnt8, Xwnt8, beta-catenin, or dominant-negative GSK3 induces the expression of neural-specific markers and inhibits the expression of Bmp4 in Xenopus ectoderm. We show that Wnt8, but...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.23.3149
更新日期:1999-12-01 00:00:00
abstract::Gene inactivation can result when a delta element of the Ty1 transposon inserted into the yeast HIS4 promoter (his4-912delta) alters the transcription initiation site. Previous work has identified mutations that suppress this transcriptional defect by restoring the transcription start site to the native position, and ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.5.604
更新日期:1996-03-01 00:00:00
abstract::Transcriptional activation of the human U1 snRNA genes is dependent on a noncanonical octamer element contained within an upstream enhancer. The U1 octamer only weakly recruits the Oct-1 POU domain, although recruitment is stimulated by a peptide containing the Oct-1-binding domain of SNAP190. Structural analysis of t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1021002
更新日期:2002-11-01 00:00:00
abstract::Medulloblastoma (MB) is the most common pediatric CNS malignancy. We identify EAG2 as an overexpressed potassium channel in MBs across different molecular and histological subgroups. EAG2 knockdown not only impairs MB cell growth in vitro, but also reduces tumor burden in vivo and enhances survival in xenograft studie...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.193789.112
更新日期:2012-08-15 00:00:00
abstract::The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.417707
更新日期:2007-05-01 00:00:00
abstract::Actin is associated with all three nuclear RNA polymerases and acts in concert with nuclear myosin I (NM1) to drive transcription. Practically nothing is known regarding the state of actin and the functional interplay of actin and NM1 in transcription. Here we show that actin and NM1 act in concert to promote RNA poly...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.455908
更新日期:2008-02-01 00:00:00
abstract::Neuronal depolarization and CaM kinase IV signaling alter the splicing of multiple exons in transcripts for ion channels, neurotransmitter receptors, and other synaptic proteins. These splicing changes are mediated in part by special CaM kinase-responsive RNA elements, within or adjacent to exons that are repressed in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1837009
更新日期:2009-10-01 00:00:00
abstract::DNA repair associated with DNA replication is important for the conservation of genomic sequence information, whereas reconstitution of chromatin after replication sustains epigenetic information. We have isolated and characterized mutations in the BRU1 gene of Arabidopsis that suggest a novel link between these under...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.295404
更新日期:2004-04-01 00:00:00
abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237628.114
更新日期:2014-05-01 00:00:00
abstract::Metazoans start embryogenesis with a relatively naïve genome. The transcriptionally inert, late-replicating heterochromatic regions, including the constitutive heterochromatin on repetitive sequences near centromeres and telomeres, need to be re-established during development. To explore the events initiating heteroch...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.272237.115
更新日期:2016-03-01 00:00:00
abstract::In response to DNA damage, cells activate a complex signal transduction network called the DNA damage response (DDR). To enhance our current understanding of the DDR network, we performed a genome-wide RNAi screen to identify genes required for resistance to ionizing radiation (IR). Along with a number of known DDR ge...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1934210
更新日期:2010-09-01 00:00:00
abstract::Chk2/hcds1, the human homolog of the Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after DNA damage. Like its yeast homologs, the Chk2/hCds1 protein phosphorylates Cdc25C in vitro, suggesting that it ar...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
abstract::We describe three strains of transgenic mice derived by embryo microinjection of DNA consisting of a long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MSV) linked to the murine c-mos coding sequences. Southern analysis of the genomic DNA of these strains suggested that in each case the transgene had integ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.10.1327
更新日期:1987-12-01 00:00:00
abstract::Persistent DNA double-strand breaks and telomeres represent genomic hazards, as they can instigate inappropriate repair reactions. Two recent papers by Oza and colleagues (pp. 912-917) and Schober and colleagues (pp. 928-938) show that both types of DNA ends are sequestered from bulk DNA by Mps3, a SUN domain protein ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1805309
更新日期:2009-05-01 00:00:00