A5022172613- Cancer-related gene regulation
- RNA modifications and cancer
- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Connective Tissue Growth Factor Research
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Wnt/β-catenin signaling in development and cancer
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Connective tissue disorders research
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- TGF-β signaling in diseases
- Nuclear Receptors and Signaling
- Zebrafish Biomedical Research Applications
- Pancreatic function and diabetes
- Cardiac electrophysiology and arrhythmias
- Retinoids in leukemia and cellular processes
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- Macrophage Migration Inhibitory Factor
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
Cardiff University
2006-2019
Moredun Research Institute
2010
University College London
2010
Cancer Research UK
2010
Institute of Cancer Research
2010
The Francis Crick Institute
2002-2004
University of Illinois Chicago
1991-2001
Medical Research Council
2001
Illinois College
1991-1997
University of Illinois Urbana-Champaign
1991-1997
Connective-tissue growth factor (CTGF) is a member of the CCN family secreted proteins. members contain four characteristic domains and exhibit multiple activities: they associate with extracellular matrix,they can mediate cell adhesion, migration chemotaxis, modulate activities peptide factors. Many effects CTGF are thought to be mediated by binding integrins, whereas others may because its recently identified ability interact BMP4 TGFβ. We demonstrate, using Xenopus embryos, that also...
Abstract The Wnt signaling pathway is frequently deregulated in cancer due to mutations genes encoding APC, β-catenin, and axin. To identify small-molecule inhibitors of as potential therapeutics, a diverse chemical library was screened using transcription factor reporter cell line which the activity induced at level Disheveled protein. A series deconvolution studies used focus on three compound that selectively killed lines with constitutive signaling. Activities compounds included ability...
ABSTRACT Tissue specification in the early embryo requires integration of spatial information at promoters developmentally important genes. Although several response elements for signalling pathways have been identified Xenopus promoters, it is not yet understood what defines sharp borders that restrict expression to a specific tissue. Here we use transgenic frog embryos study and temporal regulation Xbra promoter. Deletion analysis point mutations putative transcription factor-binding sites...
cyr6l is an immediate early gene that transcriptionally activated in 3T3 fibroblasts by serum, platelet-derived growth factor, fibroblast and the tumor promoter TPA with kinetics similar to induction of c-fos.cyr6l encodes a secreted protein associated cell surface extracellular matrix, may play role cell-cell communication.We report here complete nucleotide sequence mouse gene, which contains four short introns.The transcription start site was mapped Si nuclease primer extension analyses.A...
Cyr61 is a secreted, heparin-binding, extracellular matrix-associated protein whose activities include the promotion of adhesion and chemotaxis, stimulation fibroblast endothelial cell growth. Many, if not all, these are mediated through interactions with integrins. We explore role in early development Xenopus laevis. Gain- loss-of-function experiments show that Xcyr61 required for normal gastrulation movements. This part adhesive properties its related ability to modulate assembly matrix....
Abstract Background GATA factors 4/5/6 have been implicated in the development of heart and endodermal derivatives vertebrates. Work zebrafish has indicated that GATA5 is required for normal earlier than GATA4/6. However, knockout mouse no apparent embryonic phenotype, thereby questioning importance gene vertebrate development. Results In this study we show Xenopus embryos essential early liver precursors. addition, found GATA4 important primordia following their specification, role it might...
The earliest step in heart formation vertebrates occurs during gastrulation, when cardiac tissue is specified. Dorsoanterior endoderm thought to provide a signal that induces adjacent mesodermal cells adopt fate. However, the nature of this signalling and precise role are unknown because close proximity interdependence mesoderm gastrulation. To better define molecular events underlie induction, we have sought develop simple means inducing tissue. We show transcription factor GATA4, which has...
The cysteine-rich angiogenic protein 61 (Cyr61) is an extracellular matrix-associated, heparin-binding that mediates cell adhesion, stimulates migration, and enhances growth factor-induced proliferation. Cyr61 also promotes chondrogenic differentiation induces neovascularization. In this study, we show a 2-kb fragment of the promoter, which confers factor-inducible expression in cultured fibroblasts, able to drive accurate reporter gene lacZ transgenic mice. Thus, transgene was observed...
The mechanisms by which transcription factors, are not themselves tissue restricted, establish cardiomyocyte-specific patterns of in vivo unknown. Nor do we understand how positional cues integrated to provide regionally distinct domains gene expression within the developing heart. We describe regulation Xenopus XMLC2 gene,which encodes a regulatory myosin light chain contractile apparatus cardiac muscle. This is expressed from onset differentiation frog embryo and throughout all myocardium,...
Significance Cyclin D2 is a cell cycle regulator with spatially restricted expression. Loss and gain of function in animal models also revealed role differentiation, but the mechanisms underlying this are incompletely understood. The cardiogenic transcription factor GATA4 an upstream cyclin D2. We show that cyclinD2 part forward reinforcing loop which feeds back to enhance activity through direct interaction. Mutations abrogate interactions associated human congenital heart disease. results...
The initial genomic response to serum growth factors is the transcriptional activation of a set immediate-early genes. Serum-induced several these genes involves formation ternary complex that includes factor (SRF), 62 kDa (TCF) and element (SRE). TCF alone does not bind SRE protooncogene c-fos, but requires prior assembly SRF-SRE binary for it be recruited into complex. Here we show this an obligatory prerequisite responsive We demonstrate Elk-1, which has properties TCF, can recruit SRF on...
Transcription factor GATA4 is a critical regulator of the embryonic and postnatal heart, but mechanisms cofactors required for its diverse functions are not fully understood. Here, we show that whereas N-terminal domain inducing cardiogenesis promoting cardiomyocyte survival, distinct residues domains therein necessary to mediate these effects. Cardiogenic activity requires 24-amino-acid (aa) region (aa 129 152) which needed transcriptional synergy physical interaction with BAF60c. The same...
Background Cardiac induction, the first step in heart development vertebrate embryos, is thought to be initiated by anterior endoderm during gastrulation, but what signals are and how they act unknown. Several signaling pathways, including FGF, Nodal, BMP Wnt have been implicated cardiac specification, both gain- loss-of-function experiments. However, as these pathways regulate germ layer formation patterning, their specific roles induction difficult define. Methodology/Principal Findings To...
pip92 is an immediate early gene that transcriptionally activated in mouse 3T3 fibroblasts upon treatment with serum growth factors or the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Here we show a 73-base pair fragment located between base pairs 1231 and 1158 upstream of transcription start site sufficient to mediate transcriptional activation. This contains two binding sites for Ets family low affinity response factor. The minimal sequence mediates induction includes at least one...
Wnt/β-catenin signaling is often portrayed as a simple pathway that initiated by Wnt ligand at the cell surface leading, via linear series of interactions between 'core pathway' members, to induction nuclear transcription from genes flanked β-catenin/TCF factor binding sites. also regulated much larger set 'non-core regulators'. However relationship regulators' currently not well understood. Aberrant activation has been shown drive tumorgenesis in number different tissues. Mammalian cells...
GATA4-6 transcription factors regulate numerous aspects of development and homeostasis in multiple tissues mesodermal endodermal origin. In the heart, best studied these factors, GATA4, has distinct roles cardiac specification, differentiation, morphogenesis, hypertrophy survival. To improve understanding how GATA4 achieves its here we have focused on carboxy-terminal domain residues required for interaction with cofactors FOG2 Tbx5. We present evidence that carboxy terminal region composed...
NKCC1 is a broadly expressed Na + –K –Cl − co‐transporter involved in regulation of ion flux across the cell membrane and regulating volume. Whilst much known about activity its by protein kinases phosphatases, little activities that are independent. In this report we show over‐expression embryos Xenopus laevis induces secondary axes , independently activity. addition, results formation neural tissue ectodermal explants. We also but non‐uniformly tropicalis with prominent expression...
The mechanisms that govern specification of various cell types constitute vertebrate heart are not fully understood. Whilst most studies development have utilised the mouse embryo, we used an alternative model, embryos frog Xenopus laevis, which permits direct experimental manipulation a non-essential heart. We show in this model pluripotent animal cap explants injected with cardiogenic factor GATA4 mRNA express pan-myocardial as well ventricular and proepicardial markers. found cardiac fate...
The cysteine-rich angiogenic protein 61 (Cyr61) is an extracellular matrix-associated, heparin-binding that mediates cell adhesion, stimulates migration, and enhances growth factor-induced proliferation. Cyr61 also promotes chondrogenic differentiation induces neovascularization. In this study, we show a 2-kb fragment of the promoter, which confers factor-inducible expression in cultured fibroblasts, able to drive accurate reporter gene lacZ transgenic mice. Thus, transgene was observed...
Onecut genes belong to a family of transcription factors that are known be important in embryonic development. In the present study, we analyzed pattern expression Onecut-1/HNF6 Xenopus tropicalis using RT-PCR and whole mount situ hybridization. Expression gene was found conserved neural tube, sensory placodes anterior ventral endoderm domain consistent with developing liver primordium.