A5078393139- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Cellular Mechanics and Interactions
- Congenital heart defects research
- Hippo pathway signaling and YAP/TAZ
- Zebrafish Biomedical Research Applications
- Amino Acid Enzymes and Metabolism
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Axon Guidance and Neuronal Signaling
- Cancer-related gene regulation
- Genetic and Kidney Cyst Diseases
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Renin-Angiotensin System Studies
- Hedgehog Signaling Pathway Studies
- Polyamine Metabolism and Applications
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Hormonal Regulation and Hypertension
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- TGF-β signaling in diseases
University College London
2012-2023
University College Hospital
2007
The Francis Crick Institute
2000-2003
National Institute for Health Research
2001
Hokkaido University
1996-1999
National Cerebral and Cardiovascular Center
1990-1992
University of Tsukuba
1987-1989
Institute of Applied Biochemistry
1987
Gastrulation in the amphibian embryo is driven by cells of mesoderm. One genes that confers mesodermal identity Xenopus Brachyury (Xbra), which required for normal gastrulation movements and ultimately posterior mesoderm notochord differentiation development all vertebrates. Xbra a transcription activator, interference with activation leads to an inhibition morphogenetic during gastrulation. To understand this process, we have screened downstream target (Tada, M., Casey, E., Fairclough, L....
Collective cell migration is a mode of movement crucial for morphogenesis and cancer metastasis. However, little known about how migratory cells coordinate collectively. Here we show that mutual cell-cell attraction (named here coattraction) required to maintain cohesive clusters migrating mesenchymal cells. Coattraction can counterbalance the natural tendency disperse via mechanisms such as contact inhibition epithelial-to-mesenchymal transition. Neural crest are coattracted complement...
During vertebrate gastrulation, mesodermal and ectodermal cells undergo convergent extension, a process characterised by prominent cellular rearrangements in which polarised intercalate along the medio-lateral axis leading to elongation of antero-posterior axis. Recently, it has become evident that noncanonical Wnt/Frizzled (Fz)/Dishevelled (Dsh) signalling pathway, is related planar-cell-polarity (PCP) pathway flies, regulates extension during gastrulation. Here we isolate functionally...
Facial recognition is central to the diagnosis of many syndromes, and craniofacial patterns may reflect common etiologies. In pleiotropic Bardet-Biedl syndrome (BBS), a primary ciliopathy with intraflagellar transport dysfunction, patients have characteristic facial "gestalt" that dysmorphologists found difficult characterize. Here, we use dense surface modeling (DSM) reveal BBS mouse mutants mid-facial defects involving homologous neural crest-derived structures shared by zebrafish...
At the initial stage of carcinogenesis, transformation occurs in a single cell within an epithelial sheet. However, it remains unknown what happens at boundary between normal and transformed cells. Using Madin-Darby canine kidney (MDCK) cells with temperature-sensitive v-Src, we have examined interface Src-transformed We show that are apically extruded when surrounded by cells, but not Src alone cultured, suggesting apical extrusion cell-context-dependent manner. also observe enveloping...
In Drosophila, normal and transformed cells compete with each other for survival in a process called cell competition. However, it is not known whether comparable phenomena also occur mammals. Scribble tumor suppressor protein Drosophila this study we examine the interface between Scribble-knockdown epithelial using Madin-Darby Canine Kidney (MDCK) expressing short hairpin RNA (shRNA) tetracycline-inducible manner. We observe that undergo apoptosis are apically extruded from epithelium when...
Tight-junction-regulated actomyosin activity determines epithelial and endothelial tension on adherens junctions drives morphogenetic processes; however, whether or not tight themselves are under tensile stress is clear. Here, we use a sensor based ZO-1, scaffolding protein that links the junctional membrane to cytoskeleton, determine if carry mechanical load. Our data indicate ZO-1 forces acting regulated by extracellular matrix (ECM) stiffness adhesion molecule JAM-A. JAM-A depletion...
ABSTRACT The signaling molecule encoded by Sonic hedgehog (shh) participates in the patterning of several embryonic structures including limbs. During early fin development zebrafish, a subset cells posterior margin pectoral buds express shh. We have shown that regulation shh is consistent with role mediating activity structure analogous to zone polarizing (ZPA) (Akimenko and Ekker (1995)Dev. Biol. 170, 243 – 247). growth bony rays both paired unpaired fins, during regeneration, there does...
Coordinated morphogenetic cell movements during gastrulation are crucial for establishing embryonic axes in animals. Most recently, the non-canonical Wnt signaling cascade (PCP pathway) has been shown to regulate convergent extension Xenopus and zebrafish. Heparan sulfate proteoglycans (HSPGs) known as modulators of intercellular signaling, required vertebrates. However, function HSPGs is poorly understood. We analyze glypican 4 (Xgly4), which a member membrane-associated HSPG family. In...
Brachyury, a member of the T-box gene family, is required for posterior mesoderm and notochord differentiation in vertebrate development, mis-expression Xenopus Brachyury causes ectopic formation. transcription activator, its ability to activate essential biological function, but target genes have proved difficult identify. Here we employ hormone-inducible construct subtractive hybridization search such targets. Using this approach isolated Bix1, homeobox expressed both marginal zone vegetal...
During vertebrate gastrulation, highly coordinated cellular rearrangements lead to the formation of three germ layers, ectoderm, mesoderm and endoderm. In zebrafish, silberblick (slb)/wnt11regulates normal gastrulation movements by activating a signalling pathway similar Frizzled-signalling pathway, which establishes epithelial planar cell polarity (PCP) in Drosophila. However, mechanisms slb/wnt11 functions during zebrafish are still unclear. Using high-resolution two-photon confocal...
Wnt11 is a key signal, determining cell polarization and migration during vertebrate gastrulation. It known that functionally interacts with several signaling components, the homologues of which control planar polarity in Drosophila melanogaster. Although D. melanogaster these components are thought to polarize cells by asymmetrically localizing at plasma membrane, it not yet clear whether their subcellular localization plays similarly important role vertebrates. We show zebrafish embryonic...