A5021474533- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Tissue Engineering and Regenerative Medicine
- Zebrafish Biomedical Research Applications
- Congenital Heart Disease Studies
- Olfactory and Sensory Function Studies
- Wind Turbine Control Systems
- Epigenetics and DNA Methylation
- Craniofacial Disorders and Treatments
- Pancreatic function and diabetes
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cardiovascular Function and Risk Factors
- Coronary Artery Anomalies
- MicroRNA in disease regulation
- Angiogenesis and VEGF in Cancer
- RNA modifications and cancer
- Cancer-related gene regulation
- Health, Environment, Cognitive Aging
- Photochromic and Fluorescence Chemistry
- Birth, Development, and Health
- Cell Adhesion Molecules Research
- Galectins and Cancer Biology
- Cavitation Phenomena in Pumps
University of Sheffield
2015-2025
Hubrecht Institute for Developmental Biology and Stem Cell Research
2011-2016
University Medical Center Utrecht
2013-2016
Genomics (United Kingdom)
2016
Cancer Genomics Centre
2014
Royal Netherlands Academy of Arts and Sciences
2011
Liver, pancreas and lung originate from the presumptive foregut in temporal spatial proximity. This requires precisely orchestrated transcriptional activation repression of organ-specific gene expression within same cell. Here, we show distinct roles for chromatin remodelling factor repressor Histone deacetylase 1 (Hdac1) endodermal organogenesis zebrafish. Loss Hdac1 causes defects timely liver specification subsequent differentiation. Mosaic analyses reveal a cell-autonomous requirement...
Germline mutations in PTPN11, encoding Shp2, cause Noonan syndrome (NS) and LEOPARD (LS), two developmental disorders that are characterized by multiple overlapping symptoms. Interestingly, Shp2 catalytic activity is enhanced NS reduced LS mutations. Defective cardiac development a prominent symptom of both LS, but how the variants affect unclear. Here, we have expressed most common Shp2-variants zebrafish embryos to investigate their role vivo. Heart function was impaired expressing Shp2....
In vertebrates, left-right (LR) axis specification is determined by a ciliated structure in the posterior region of embryo. Fluid flow this responsible for induction unilateral left-sided Nodal activity lateral plate mesoderm, which turn regulates organ laterality. Bmp signalling has been implied repressing expression on right side, however its mechanism action controversial. forward genetic screen mutations that affect LR patterning, we identified zebrafish linkspoot (lin) mutant,...
Vertebrate heart development requires the complex morphogenesis of a linear tube to form mature organ, process essential for correct cardiac and function, requiring coordination embryonic laterality, growth, regionalized cellular changes. While previous studies have demonstrated broad requirements extracellular matrix (ECM) components in morphogenesis, we hypothesized that ECM regionalization may fine tune shape during development.Using live vivo light sheet imaging zebrafish embryos,...
Heart development involves the complex structural remodelling of a linear heart tube into an asymmetrically looped and ballooned organ. Previous studies have associated regional expansion extracellular matrix (ECM) space with tissue morphogenesis during development. We developed morphoHeart, 3D segmentation morphometry software user-friendly graphical interface (GUI) that delivers first integrated visualisation multiparametric analysis both ECM morphology in live embryos. morphoHeart reveals...
Pattern formation is fundamental to embryonic morphogenesis. In the zebrafish heart, spatially confined single-cell delamination in ventricle outer curvature initiates trabeculation, a conserved morphogenetic process critical for heart function and life. Yet, what confines remains ill-understood. Contrary prevailing notion of patterning through biochemical signals, we now show that mechanical fracturing cardiac extracellular matrix (cECM) patterns curvature. cECM fractures emerge...
Establishing correct left–right asymmetry during embryonic development is crucial for proper asymmetric positioning of the organs. Congenital heart defects, such as dextrocardia, transposition arteries, and inflow or outflow tract malformations, comprise some most common birth defects may be attributed to incorrect establishment body laterality. Here, we identify new patients with dextrocardia who have mutations in CFAP53, a coiled-coil domain containing protein. To elucidate mechanism by...
ABSTRACT Cadherin complexes mediate cell-cell adhesion and are crucial for embryonic development. Besides their structural function, cadherin also transduce tension across the junction-actomyosin axis into proportional biochemical responses. Central to this mechanotransduction is stretching of cadherin-F-actin-linker α-catenin, which opens its central domain binding effectors such as vinculin. Mechanical unfolding α-catenin leads force-dependent reinforcement cadherin-based junctions studied...
Summary Heart development involves the complex structural remodelling of a linear heart tube into an asymmetrically looped and ballooned organ. Previous studies have associated regional expansion extracellular matrix (ECM) space with tissue morphogenesis during development. We developed morphoHeart , 3D image segmentation morphometry software which delivers first integrated visualisation multiparametric analysis both ECM morphology in live embryos. reveals that undergoes dynamic reduction...
During early vertebrate heart development, the transitions from a linear tube to complex asymmetric structure, morphogenetic process that occurs simultaneously with growth of heart. Cardiac during morphogenesis is driven by deployment cells second field (SHF) into both poles Laminin core component extracellular matrix and, although mutations in laminin subunits are linked cardiac abnormalities, no role for has been identified morphogenesis. We tissue-specific expression genes developing...
Abstract Local haemodynamics control arterial homeostasis and dysfunction by generating wall shear stress (WSS) which regulates endothelial cell (EC) physiology. Here we use a zebrafish model to identify genes that regulate EC proliferation in response flow. Suppression of blood flow embryos (by targeting cardiac troponin) reduced the intersegmental vessels (ISVs) compared controls exposed The expression candidate regulators was analysed isolated from qRT-PCR. Genes shown be expressed were...
ABSTRACT During heart development, the embryonic ventricle becomes enveloped by epicardium, which adheres to outer apical surface of heart. This is concomitant with onset ventricular trabeculation, where a subset cardiomyocytes lose apicobasal polarity and delaminate basally from wall. Llgl1 regulates formation cell junctions polarity, we investigated its role in wall maturation. We found that llgl1 mutant zebrafish embryos exhibit aberrant extrusion cardiomyocytes. While investigating...
Abstract The mature vertebrate heart develops from a simple linear cardiac tube during early development through series of highly asymmetric morphogenetic processes including looping and chamber ballooning. While the directionality morphogenesis is partly controlled by embryonic laterality signals, previous studies have suggested that these extrinsic cues interact with tissue-intrinsic signals in to ensure robust morphogenesis. Using live vivo imaging zebrafish embryos we describe...