107 results match your criteria: "MRC Centre for Developmental and Biomedical Genetics[Affiliation]"
Development
September 2011
MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Specification of the otic anteroposterior axis is one of the earliest patterning events during inner ear development. In zebrafish, Hedgehog signalling is necessary and sufficient to specify posterior otic identity between the 10 somite (otic placode) and 20 somite (early otic vesicle) stages. We now show that Fgf signalling is both necessary and sufficient for anterior otic specification during a similar period, a function that is completely separable from its earlier role in otic placode induction.
View Article and Find Full Text PDFMethods Mol Biol
November 2011
MRC Centre for Developmental and Biomedical Genetics, The University of Sheffield, Sheffield, UK.
A key feature of inflammatory cells is the ability to migrate to a site of injury or infection quickly and efficiently. Infectious agents can then be taken up by these inflammatory cells, preventing established infection. Inflammatory cell migration is driven by a complex interaction between inflammatory cells and their environment.
View Article and Find Full Text PDFZebrafish
September 2011
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, United Kingdom.
Zebrafish are increasingly used to study neurodegenerative conditions such as Parkinson's disease (PD). In rodents, the influence of the genetic background on important experimental parameters in PD research such as susceptibility to toxin exposure or motor behavior is well established. In contrast, little is known about the impact of the genetic background in commonly used zebrafish wild-type strains on these important experimental parameters.
View Article and Find Full Text PDFBirth Defects Res C Embryo Today
June 2011
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, UK.
The zebrafish is emerging as a novel model for the study of embryonic vascular development. In this review we summarize the advantages of this intriguing experimental system and the advances in our understanding of the molecular control of vascular development it has allowed.
View Article and Find Full Text PDFDevelopment
June 2011
MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
The infundibulum links the nervous and endocrine systems, serving as a crucial integrating centre for body homeostasis. Here we describe that the chick infundibulum derives from two subsets of anterior ventral midline cells. One set remains at the ventral midline and forms the posterior-ventral infundibulum.
View Article and Find Full Text PDFBlood
July 2011
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, United Kingdom.
The oxygen-sensing transcription factor hypoxia-inducible factor-1α (HIF-1α) plays a critical role in the regulation of myeloid cell function. The mechanisms of regulation are not well understood, nor are the phenotypic consequences of HIF modulation in the context of neutrophilic inflammation. Species conservation across higher metazoans enables the use of the genetically tractable and transparent zebrafish (Danio rerio) embryo to study in vivo resolution of the inflammatory response.
View Article and Find Full Text PDFDevelopment
May 2011
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, S10 2TN, UK.
The size, composition and functioning of the spinal cord is likely to depend on appropriate numbers of progenitor and differentiated cells of a particular class, but little is known about how cell numbers are controlled in specific cell cohorts along the dorsoventral axis of the neural tube. Here, we show that FatJ cadherin, identified in a large-scale RNA interference (RNAi) screen of cadherin genes expressed in the neural tube, is localised to progenitors in intermediate regions of the neural tube. Loss of function of FatJ promotes an increase in dp4-vp1 progenitors and a concomitant increase in differentiated Lim1(+)/Lim2(+) neurons.
View Article and Find Full Text PDFDev Cell
April 2011
MRC Centre for Developmental and Biomedical Genetics, and Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
The core planar polarity proteins localize asymmetrically to the adherens junctions of epithelial cells, where they have been hypothesized to assemble into intercellular complexes. Here, we show that the core proteins are preferentially distributed to discrete membrane subdomains ("puncta"), where they form asymmetric contacts between neighboring cells. Using an antibody internalization assay and fluorescence recovery after photobleaching in prepupal and pupal wings, we have investigated the turnover of two key core proteins, Flamingo and Frizzled, and find that the localization of both within puncta is highly stable.
View Article and Find Full Text PDFCurr Neurol Neurosci Rep
June 2011
MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Sciences, University of Sheffield, Sheffield S102TN, UK.
PINK1 is a mitochondrially targeted kinase that has been linked to a rare monogenic form of Parkinson's disease (PD), a common neurodegenerative disease characterized by the degeneration of selected dopaminergic neurons. Intensive research using many model systems has clearly established a fundamental role for PINK1 in preventing mitochondrial dysfunction-a key mechanism long thought to play a central role in PD pathogenesis. Current hypotheses propose PINK1's important functions involve mitophagy, mitochondrial calcium buffering, and mitochondrial quality control.
View Article and Find Full Text PDFAdv Genet
June 2011
MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder principally affecting the dopaminergic neurons of the substantia nigra. The pathogenic mechanisms are unknown and there are currently no cure or disease-modifying therapies. Recent genetic linkage studies have begun to identify single-gene mutations responsible for rare heritable forms of PD and define genetic risk factors contributing to disease prevalence in sporadic cases.
View Article and Find Full Text PDFPLoS One
January 2011
MRC Centre for Developmental and Biomedical Genetics, School of Medicine and Biomedical Science, The University of Sheffield, Sheffield, United Kingdom.
Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF.
View Article and Find Full Text PDFCell Signal
May 2011
MRC Centre for Developmental and Biomedical Genetics, The University of Shefield, Firth Court, Shefield, S10 2TN, UK.
JAK/STAT signalling in vertebrates is activated by multiple cytokines and growth factors. By contrast, the Drosophila genome encodes for only three related JAK/STAT ligands, Upd, Upd2 and Upd3. Identifying the differences between these three ligands will ultimately lead to a greater understanding of this disease-related signalling pathway and its roles in development.
View Article and Find Full Text PDFBMC Genomics
January 2011
MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom.
Background: The epigenetic regulator Histone Deacetylase 1 (Hdac1) is required for specification and patterning of neurones and myelinating glia during development of the vertebrate central nervous system (CNS). This co-ordinating function for Hdac1 is evolutionarily conserved in zebrafish and mouse, but the mechanism of action of Hdac1 in the developing CNS is not well-understood.
Results: A genome-wide comparative analysis of the transcriptomes of Hdac1-deficient and wild-type zebrafish embryos was performed, which identified an extensive programme of gene expression that is regulated by Hdac1 in the developing embryo.
Thromb Haemost
May 2011
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, UK.
The zebrafish is an outstanding model for intravital imaging of inflammation due to its optical clarity and the ability to express fluorescently labelled specific cell types by transgenesis. However, although several transgenic labelling myeloid cells exist, none allow distinction of macrophages from neutrophils. This prevents simultaneous imaging and examination of the individual contributions of these important leukocyte subtypes during inflammation.
View Article and Find Full Text PDFBMC Biol
December 2010
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
The zebrafish is proving to be an extremely versatile new experimental model for unraveling the mysteries of innate immunity and has considerable promise as a system for the identification of novel modulators of this crucial biological process. A rate-limiting factor, however, is the mechanical stimulus required to induce the inflammatory response. A new chemically induced inflammation assay ('ChIn' assay) published in BMC Biology obviates this requirement and seems set to accelerate progress in the field.
View Article and Find Full Text PDFMech Dev
June 2011
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, UK.
In tetrapod long bones, Hedgehog signalling is required for osteoblast differentiation in the perichondrium. In this work we analyse skeletogenesis in zebrafish larvae treated with the Hedgehog signalling inhibitor cyclopamine. We show that cyclopamine treatment leads to the loss of perichondral ossification of two bones in the head.
View Article and Find Full Text PDFSci Signal
November 2010
Medical Research Council (MRC) Centre for Developmental and Biomedical Genetics, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Endocytosis modulates the activities of members of a family of receptors known as Frizzled (Fz) proteins, which control canonical β-catenin signaling and the planar cell polarity pathway; however, what determines which of the two pathways is activated is unclear. Evidence now suggests that the guanosine triphosphatase Rab5, a key regulator of endocytosis, binds directly to Fz proteins and that subsequent trafficking steps determine the outcome of Fz signaling.
View Article and Find Full Text PDFJ Cell Sci
October 2010
MRC Centre for Developmental and Biomedical Genetics, The University of Sheffield, Firth Court, Sheffield S102TN, UK.
Appropriate regulation of signal transduction pathways is essential for normal development and is often disrupted in disease. Therefore, many regulatory mechanisms and feedback loops have evolved to ensure appropriate signalling. One mechanism previously suggested to modulate a range of signal transduction pathways involves the internalisation and destruction of transmembrane receptors by the endocytic trafficking machinery.
View Article and Find Full Text PDFDis Model Mech
February 2011
MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, UK.
Mutations in the SPAST (SPG4) gene, which encodes the microtubule-severing protein spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP). Following on from previous work in our laboratory showing that spastin is required for axon outgrowth, we report here that the related microtubule-severing protein katanin is also required for axon outgrowth in vivo. Using confocal time-lapse imaging, we have identified requirements for spastin and katanin in maintaining normal axonal microtubule dynamics and growth cone motility in vivo, supporting a model in which microtubule severing is required for concerted growth of neuronal microtubules.
View Article and Find Full Text PDFDev Dyn
June 2010
MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, UK.
On October 29, 2009, researchers and physicians gathered at the Sheraton Four Points Hotel in Boston for 4 days to discuss a disease called multiple hereditary exostoses (MHE). MHE is an autosomal dominant disease that is associated with mutations in two enzymes that are required for heparan sulfate (HS) synthesis. Children with the disease form numerous benign bone tumors (osteochondromas) and have >2% chance of developing chondrosarcoma.
View Article and Find Full Text PDFAutophagy
July 2010
MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Sciences, University of Sheffield, Sheffield, UK.
Much evidence links mitochondrial dysfunction to the death of neurons in Parkinson disease (PD), and is particularly emphasized by our growing understanding of the function of genes linked to recessively inherited PD such as PINK1, parkin and DJ-1. Recent work has revealed an exciting link between the PINK1-Parkin pathway and the autophagic turnover of dysfunctional mitochondrial (mitophagy). We have recently shown that mitofusin is ubiquitinated by Parkin when it is recruited to dysfunctional mitochondria.
View Article and Find Full Text PDFCurr Biol
May 2010
Medical Research Council (MRC) Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
The Drosophila genes fat (ft) and dachsous (ds) encode large atypical cadherins that collaborate to coordinately polarize cells in the plane of the epithelium (planar cell polarity) and to affect growth via the Warts/Hippo pathway. Ft and Ds form heterodimeric bridges that convey polarity information from cell to cell. four-jointed (fj) is a modulator of Ft/Ds activity that acts in a graded fashion in the abdomen, eye, and wing.
View Article and Find Full Text PDFDevelopment
April 2010
MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield, UK.
In zebrafish, Hedgehog (Hh) signalling from ventral midline structures is necessary and sufficient to specify posterior otic identity. Loss of Hh signalling gives rise to mirror symmetric ears with double anterior character, whereas severe upregulation of Hh signalling leads to double posterior ears. By contrast, in mouse and chick, Hh is predominantly required for dorsoventral otic patterning.
View Article and Find Full Text PDFDevelopment
February 2010
MRC Centre for Developmental and Biomedical Genetics, Addison Building, Western Bank, University of Sheffield, Sheffield, S10 2TN, UK.
Although the regulation of osteoblast and adipocyte differentiation from mesenchymal stem cells has been studied for some time, very little is known about what regulates their appearance in discrete regions of the embryo. Here we show that, as in other vertebrates, zebrafish osteoblasts and adipocytes originate in part from cephalic neural crest (CNC) precursors. We investigated the roles that the retinoic acid (RA) and Peroxisome proliferator-activated receptor gamma (Pparg) pathways play in vivo and found that both pathways act on CNC to direct adipocyte differentiation at the expense of osteoblast formation.
View Article and Find Full Text PDFCold Spring Harb Perspect Biol
November 2009
MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, United Kingdom.
In addition to specifying cell fate, there is a wealth of evidence that molecular gradients are also primarily responsible for specifying cell polarity, particularly in the plane of epithelial sheets ("planar polarity"). The first compelling evidence of a role for gradients in specifying planar polarity came from transplantation experiments in the insect cuticle. More recent molecular genetic analyses in the fruit fly Drosophila have begun to give insights into the molecular nature of the gradients involved, and how they are interpreted at the cellular level.
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