- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Tissue Engineering and Regenerative Medicine
- Animal Genetics and Reproduction
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Pancreatic function and diabetes
- RNA modifications and cancer
- Liver physiology and pathology
- Vector-borne infectious diseases
- Congenital Heart Disease Studies
- Invertebrate Immune Response Mechanisms
- Nutrition, Genetics, and Disease
- Invertebrate Taxonomy and Ecology
- Autism Spectrum Disorder Research
- Ion Channels and Receptors
- Cardiac Fibrosis and Remodeling
- Membrane-based Ion Separation Techniques
- Silk-based biomaterials and applications
University of Aberdeen
2014-2024
Institute of Medical Sciences
2014-2022
University of East Anglia
2001-2016
Norwich Research Park
2016
University of Dundee
1999-2002
Wellcome Trust
1999-2001
University of Washington
1996-1998
Howard Hughes Medical Institute
1997
MRC Laboratory of Molecular Biology
1994-1996
Medical Research Council
1994
During gastrulation of Xenopus embryos the prospective mesoderm is induced initially with domains dorsal and ventral fate, then further patterned to generate somitic by signals from gastrula organizer. Although Xwnt-8 expressed in future ventrolateral induces epidermis differentiate vitro as mesoderm, no loss-of-function studies have demonstrated a requirement for Wnt signaling normal expression mesodermal genes gastrula. We report development dominant-negative (dnXwnt-8) that inhibits...
Developmental signalling pathways operate repeatedly to regulate remarkably tissue- and stage-specific transcriptional responses. Canonical Wnt/β‑catenin is such a key developmental pathway; however, while recruitment of nuclear β-catenin target genomic loci serves as the hallmark canonical Wnt signalling, mechanisms controlling context-specific responses in different stages tissues remain elusive. Here using first direct comparison genome-wide occupancy β‑catenin with stage-matched...
Wnt signaling is a key regulator of vertebrate heart development; however, specific roles for human cardiomyocyte development remain uncertain. Here we use embryonic stem cells (hESCs) to analyze systematically in the expression endogenous components, monitor pathway activity, and dissect stage-specific requirements canonical noncanonical mechanisms using small-molecule inhibitors. Our analysis suggests that WNT3 WNT8A, via FZD7 signaling, regulate BRACHYURY mesoderm induction; WNT5A/5B,...
Tcf/Lef transcription factors and beta-catenin mediate canonical Wnt signalling, which plays remarkably diverse roles in embryonic development, stem cell renewal cancer progression. To investigate the molecular mechanisms allowing for these yet specific functions, we studied several distinct Wnt/beta-catenin signalling early Xenopus development: establishing dorsal body axis; regulating mesoderm induction; subsequent ventrolateral patterning. Our previous experiments expression patterns of...
Cardiogenesis is inhibited by canonical Wnt/beta-catenin signalling and stimulated non-canonical Wnt11/JNK signalling, but how these two pathways crosstalk currently unknown. Here, we show that restricts cardiogenesis via inhibition of GATA gene expression, as experimentally reinstating function overrides beta-catenin-mediated restores cardiogenesis. Furthermore, transcription factors in turn directly regulate Wnt11 required to a significant degree for mediating the cardiogenesis-promoting...
dishevelled, shaggy/zeste-white 3 and armadillo are required for transmission of the wingless signal in Drosophila epidermis. We show that these genes act same epistatic order embryonic midgut to transmit signal. In addition mediating transcriptional stimulation homeotic Ultrabithorax labial, they also repression labial by high levels. Efficient expression thus only occurs within a window intermediate pathway activity. Finally, mutants revealed signalling can stimulate decapentaplegic...
Wnt signalling is a key regulator of vertebrate heart development, yet it unclear which specific components are required to regulate aspect cardiogenesis. Previously, we identified Wnt6 as an endogenous ligand for controlling muscle differentiation via canonical Wnt/β-catenin signalling. Here show the first time requirement inhibitor normal differentiation. Expression sfrp1 strongly induced in differentiating muscle. We that not only able promote but also formation size embryo. functionally...
Wnt signalling functions in many tissues and during different stages of animal development to produce very specific responses. In early Xenopus embryos there is a dramatic change response within only few hours development. leads dorsalising response, which establishes the endogenous dorsal axis. Only later development, almost opposite happens: Xwnt-8 pattern embryonic mesoderm by promoting ventral lateral mesoderm. The specificity could conceivably be carried out differential use signal...
Mesodermal tissue with heart forming potential (cardiogenic mesoderm) is induced during gastrulation. This cardiogenic mesoderm later differentiates into muscle (myocardium) and non-muscular tissue. Inhibition of Wnt/beta-catenin signaling known to be required early for induction mesoderm; however, the identity inhibiting Wnt signal itself still elusive. We have identified Wnt6 in Xenopus as an endogenous signal, which expressed tissues close inside developing heart. Our loss-of-function...
Developmentally, the pancreas and liver are closely related pathological conditions - including elevated glucocorticoid levels result in appearance of hepatocytes pancreas. The role WNT signalling pathway this process has been examined model transdifferentiating pancreatic acinar AR42J-B-13 (B-13) cell. Glucocorticoid treatment resulted a transient loss constitutive WNT3a expression, phosphorylation depletion beta-catenin, beta-catenin nuclear localisation, significant reductions T-cell...
Abstract A functioning heart muscle is required continuously throughout life. During embryonic development the tissue differentiates from mesoderm that has heart‐forming potential. Heart‐forming potential in regulated by pro‐cardiogenic transcription factors, such as members of GATA and NK‐2 factor families. Subsequent differentiation involves expression cytoskeletal proteins, including myosins troponins. Different Wnt signalling pathways have various functions development. So‐called...