A5004745599- Congenital heart defects research
- Developmental Biology and Gene Regulation
- Renal and related cancers
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Pregnancy and preeclampsia studies
- Genomics and Chromatin Dynamics
- Neurogenesis and neuroplasticity mechanisms
- RNA modifications and cancer
- Skin and Cellular Biology Research
- Genomics and Rare Diseases
- Congenital Heart Disease Studies
- Cell Image Analysis Techniques
- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- Silk-based biomaterials and applications
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Genomic variations and chromosomal abnormalities
- Cell Adhesion Molecules Research
- Nuclear Structure and Function
- Cardiovascular Issues in Pregnancy
- Zebrafish Biomedical Research Applications
- Molecular Biology Techniques and Applications
- Acute Ischemic Stroke Management
The Francis Crick Institute
2016-2023
University of Oxford
2019
Imperial College London
2016-2017
Jackson Laboratory
2017
Medical Research Council
2014
King's College London
2003-2005
Université Joseph Fourier
1997-2004
Institut pour l'avancée des biosciences
1997-2004
Centre National de la Recherche Scientifique
1997-2004
Placental heart development and embryonic occur in parallel, these organs have been proposed to exert reciprocal regulation during gestation. Poor placentation has associated with congenital disease, an important cause of infant mortality. However, the mechanisms by which altered placental can lead disease remain unresolved.
We report a recurrent CNOT1 de novo missense mutation, GenBank: NM_016284.4; c.1603C>T (p.Arg535Cys), resulting in syndrome of pancreatic agenesis and abnormal forebrain development three individuals similar phenotype mice. is transcriptional repressor that has been suggested as being critical for maintaining embryonic stem cells pluripotent state. These findings suggest plays role neurological describe novel genetic holoprosencephaly. Discovering genes with mutations causal crucial to...
The Hippo-YAP/TAZ pathway is an important regulator of tissue growth, but can also control cell fate or morphogenesis. Here we investigate the function Hippo during development cartilage, which forms majority skeleton. Previously, YAP was proposed to inhibit skeletal size by repressing chondrocyte proliferation and differentiation. We find that, in vitro, Yap/Taz double knockout impairs proliferation, whilst constitutively nuclear nls-YAP5SA accelerates line with canonical role this most...
Abstract Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence 0.9% births. However, two-thirds cases have an unknown cause, and many these are thought to be caused by in utero exposure environmental teratogens. Here we identify potential teratogen causing CHD mice: maternal iron deficiency (ID). We show that ID mice causes severe cardiovascular defects offspring. These likely arise from increased retinoic acid signalling embryos. The can prevented...
<ns4:p><ns4:bold>Background:</ns4:bold> Identifying genes that are essential for mouse embryonic development and survival through term is a powerful unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in embryos result from ablation lethal necessary first step towards uncovering their role normal establishing any correlates amongst congenital abnormalities.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> Here we present results...
Nuclear envelope integrity is essential for the compartmentalization of nucleus and cytoplasm. Importantly, mutations in genes encoding nuclear (NE) associated proteins are second highest cause familial dilated cardiomyopathy. One such NE protein that causes cardiomyopathy humans affects mouse heart development Lem2. However, its role remains poorly understood.We generated mice which Lem2 was specifically ablated either embryonic cardiomyocytes (Lem2 cKO) or adult iCKO) carried out detailed...
Abstract The interplay between 3D chromatin architecture and gene silencing is incompletely understood. Here, we report a novel point mutation in the non-canonical SMC protein SMCHD1 that enhances its capacity at endogenous developmental targets. Moreover, it also results enhanced facioscapulohumeral muscular dystrophy associated macrosatellite-array, D4Z4 , resulting repression of DUX4 encoded by this repeat. Heightened perturbs Hox activation, causing homeotic transformation mice....
We have investigated the mechanisms involved in generating hindbrain motoneurone subtypes, focusing on somatic motoneurones, which are confined to caudal within rhombomeres 5-8. Following heterotopic transplantation of along rostrocaudal axis at various developmental stages, we found that capacity generate motoneurones is labile neural plate stage but becomes fixed just after tube closure, 10-11. Grafting somites or retinoic acid-loaded beads beneath rostral induced formation rhombomere 4...
Hox genes encode a conserved family of homeodomain transcription factors regulating development along the major body axis. During embryogenesis, proteins are expressed in segment-specific patterns and control numerous different cell fates. It has been unclear, however, whether drive epithelial segregation mechanism that is thought to initiate segmentation process. Here, we investigate role vertebrate during partitioning developing hindbrain into lineage-restricted units called rhombomeres....
We present a simple and quick system for accurately scoring the developmental progress of mouse embryos harvested on embryonic day 14 (E14.5). Based solely external appearance maturing forelimb, we provide convenient way to distinguish six sub-stages. Using variety objective morphometric data obtained from commonly used C57BL/6N strain, show that these stages correlate precisely with growth entire embryo its organs. Applying new staging phenotype analyses E14.5 58 lethal null mutant lines...
We studied the expression of two distantly clustered Hox genes which could, respectively, be involved in specification dorsal feather- and foot scale-forming skin chick embryo: cHoxc-8, a median paralog, cHoxd-13, located at 5′ extremity HoxD cluster. The cHoxc-8 transcripts are present embryonic day 3.5 (E3.5)in somitic cells, give rise to dermis by E5, E6.5–8.5 dermal epidermal cells during first stages feather morphogenesis. cHoxd-13 E4.5–9.5 autopodial mesenchyme E10.5–12.5 plantar...
<ns4:p><ns4:bold>Background:</ns4:bold> Identifying genes that are essential for mouse embryonic development and survival through term is a powerful unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in embryos result from ablation lethal necessary first step towards uncovering their role normal establishing any correlates amongst congenital abnormalities.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> Here we present results...
Abstract Accurate identification of abnormalities in the mouse embryo depends not only on comparisons with appropriate, developmental stage‐matched controls, but also an appreciation range anatomical variation that can be expected during normal development. Here we present a morphological, topological and metric analysis heart arteries embryos harvested embryonic day (E)14.5, based digital volume data whole analysed by high‐resolution episcopic microscopy ( HREM ). By comparing from 206...
The Deciphering the Mechanisms of Developmental Disorders (DMDD) program uses a systematic and standardised approach to characterise phenotype embryos stemming from mouse lines, which produce embryonically lethal offspring. Our study aims provide detailed descriptions homozygous Col4a2em1(IMPC)Wtsi mutants produced in DMDD harvested at embryonic day 14.5. This shall new information on role Col4a2 plays organogenesis demonstrate capacity database for identifying models researching inherited...
The vacuolar protein sorting-associated 13B (VPS13B) is a large and highly conserved protein. Disruption of VPS13B causes the autosomal recessive Cohen syndrome, rare disorder characterized by microcephaly intellectual disability among other features, including developmental delay, hypotonia, friendly-personality. However, underlying mechanisms which disruption leads to brain dysfunction still remain unexplained. To gain insights into neuropathogenesis we systematically changes in...
Abstract The dorsal and ventral scales of the chick foot can be distinguished morphologically molecularly: oblong overlapping scuta expressing both α β keratins, roundish nonprotruding reticula only keratins. question arises how En‐1 Lmx1 , whose role in dorsoventral limb patterning has been well established, affect skin morphogenesis, which occurs 8 to 12 days later. Forced expression or hindlimb have, respectively, as expected, a ventralizing dorsalizing effect on skin, leading formation...
Abstract Approximately one‐third of randomly produced knockout mouse lines produce homozygous offspring, which fail to survive the perinatal period. The majority these die around or after embryonic day (E)14.5, presumably from cardiovascular insufficiency. For diagnosing structural abnormalities underlying death and diseases for researching gene function, phenotype individuals has be analysed. This makes creation reference data, define normal anatomy variations highest priority. While such...
The protein kinase PKN2 is required for embryonic development and knockout mice die as a result of failure in the expansion mesoderm, cardiac neural tube closure. In adult, cardiomyocyte PKN1 (in combination) are adaptation to pressure-overload. specific role contractile cardiomyocytes during its adult heart remain be fully established. We used with cardiomyocyte-directed or global haploinsufficiency assess function using high resolution episcopic microscopy, MRI, micro-CT echocardiography....
High resolution episcopic microscopy (HREM) produces digital volume data by physically sectioning histologically processed specimens, while capturing images of the subsequently exposed block faces. Our study aims to systematically define spectrum typical artefacts inherent HREM and research their effect on interpretation phenotype wildtype mutant mouse embryos. A total 607 (198 wildtypes, 409 mutants) sets embryos harvested at embryonic day (E) 14.5 were comprehensively examined. The...