A5006824297- Developmental Biology and Gene Regulation
- Hippo pathway signaling and YAP/TAZ
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Hedgehog Signaling Pathway Studies
- Wnt/β-catenin signaling in development and cancer
- Renal and related cancers
- Gene expression and cancer classification
- Retinal Development and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Animal Genetics and Reproduction
- Retinal Diseases and Treatments
- Axon Guidance and Neuronal Signaling
- Machine Learning and Data Classification
- Hair Growth and Disorders
- Lung Cancer Research Studies
- Tissue Engineering and Regenerative Medicine
- Congenital limb and hand anomalies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Helicobacter pylori-related gastroenterology studies
- MicroRNA in disease regulation
- Neuroblastoma Research and Treatments
- Retinal and Macular Surgery
- Microtubule and mitosis dynamics
University of Sheffield
2000-2020
Western General Hospital
1996-2002
University of Edinburgh
1993
Physiological Society
1988
Distinct classes of motor neurons and ventral interneurons are generated by the graded signaling activity Sonic hedgehog (Shh). Shh controls neuronal fate establishing different progenitor cell populations in neural tube that defined expression Pax6 Nkx2.2. establishes distinct identity interneurons, mediating spinal cord hindbrain.
Abstract Post-mitotic neurons generated at the rhombic lip undertake long distance migration to widely dispersed destinations, giving rise cerebellar granule cells and precerebellar nuclei. Here we show that Pax6, a key regulator in CNS eye development, is strongly expressed migrating away from it. Development of some structures derived these severely affected Pax6-null Small (Pax6Sey/Pax6Sey) embryos. Cell proliferation initial differentiation seem unaffected, but cell neurite extension are...
In the proliferative zone of developing cerebral cortex, multipotential progenitors predominate early in development and divide to increase progenitor pool. As corticogenesis progresses, proportionately fewer are produced and, instead, cell divisions yield higher numbers postmitotic neurones or glial cells. switch from generation that differentiated cells occurs, orientation division alters predominantly symmetrical asymmetrical. It has been hypothesised expand pool, whereas asymmetrical...
Loss of Crumbs homologue 1 (CRB1) function causes either the eye disease Leber congenital amaurosis or progressive retinitis pigmentosa, depending on amount residual CRB1 activity and genetic background. Crb1 localizes specifically to sub-apical region adjacent adherens junction complex at outer limiting membrane in retina. We show that it is associated here with multiple PDZ protein (Mupp1), Lin-7 (Pals1 Mpp5) Mpp4. have produced Crb1(-/-) mice completely lacking any functional Crb1....
ABSTRACT Mouse embryos that are homozygous for the Brachyury (T) deletion die at mid-gestation. They have prominent defects in notochord, allantois and primitive streak. Expression of T gene commences onset gastrulation is restricted to streak, mesoderm emerging from head process notochord. Genetic evidence has suggested there may be an increasing demand function along rostrocaudal axis. Experiments reported here indicate this not case. Instead, gradient severity defect caused by defective...
In humans, the Crumbs homolog-1 (CRB1) gene is mutated in progressive types of autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. However, there no clear genotype–phenotype correlation for CRB1 mutations, which suggests that other components CRB complex may influence severity retinal disease. Therefore, to understand physiological role proteins, we generated analysed conditional knockout mice lacking CRB2 developing retina. Progressive disorganization was detected...
To investigate T(Brachyury) gene function, a chimeric analysis of midgestation (9.5-11.5 days post coitum) embryos has been performed. Embryonic stem (ES) cell lines homozygous or heterozygous for the T have introduced into wild-type host by blastocyst injection, and resulting chimeras scored morphological abnormality extent colonization T/T cells. As observed previously in earlier stage (Rashbass, P., Cooke, L. A., Herrmann, B. G. Beddington, R. S. P. (1991) Nature 353, 348-350), 9.5-11.5...
Abstract The murine homolog of the multiple endocrine neoplasia type 1 (MEN1) gene (men1), which in humans is associated with tumors parathyroids, pancreas, and pituitary, has been characterized by isolating 27 clones from a mouse embryonic stem cell cDNA library. insert sizes ranged 600–2500 bp, sequence analysis identified 1833 bp open reading frame encoding 611 amino acid protein. In addition, two contained an unspliced intron 1, another 20–29 upstream sequence, suggested presence...
Abstract Motivation: Gene expression levels are obtained from microarray experiments through the extraction of pixel intensities a scanned image slide. It is widely acknowledged that variabilities can occur in extracted same images by different users with software packages. These inconsistencies arise due to differences refinement placement ‘grids’. We introduce novel automated approach grid placements based upon use Bayesian inference for determining size, shape and positioning ‘spots’,...
Abstract The mouse nude mutation inactivates the gene encoding Foxn1 transcription factor, causing defective hair morphogenesis. Here, we show for first time that is required proper assembly of medulla, and identify Foxn1‐regulated genes by transcript profiling. One such encodes desmosomal cadherin, Dsc2. Significantly, Foxn1‐dependent Dsc2 expression restricted to within these cells, protein predominantly localized specialized adhesion junctions between cortex medulla. Our results reveal as...
Abstract ESCs undergoing neural differentiation in vitro display an intrinsic heterogeneity with a large subset of the cells forming polarized rosettes that maintain progenitor microenvironment. This is not only necessary for normal development but also causes substantial technical challenges practical applications. Here, we report novel regulator early progenitors, apical polarity protein Crb2 (Crumbs homologue 2). Employing monolayer mouse to model neurogenesis vitro, find upregulated Sox1...
The origin of different mesodermal tissues during gastrulation and the developmental lability precursors can be mapped by transplanting marked epiblast cells to same or a position in host egg cylinder, assessing subsequent fate transplanted tissue. This information provides context for role particular patterns gene expression mesoderm formation differentiation. For example, stability Hox examined transgenically somites that express somite file where it is not normally expressed. Such...
In the spinal cord, central canal forms through a poorly understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer (VL) cells. Here, we use mouse chick models to show (dVL) cells adjacent midline Nestin(+) radial glia (dmNes+RG) down-regulate apical polarity proteins, including Crumbs2 (CRB2) delaminate in stepwise manner; live imaging shows as one cell delaminates, next ratchets up, dmNes+RG endfoot down, repeats. We secrete...
Abstract The effects of 40, 50, and 60 mg/kg streptozotocin (SZ) on the body weights glucose concentration osmolarity serum adult rats were determined. Serum prepared from these SZ‐dosed was used in embryo culture experiments to investigate diabetic rat embryos during organogenesis. resulting each tested doses SZ teratogenic 9.5‐day explants (embryos their membranes), causing a range dysmorphic lesions including cranofacial defects, heart abnormalities branchial arches otic capsules....
Gene expression measurements quantify the level of mRNA produced from each gene. Two principal methods exist for producing slides extracting these levels: photolithography and spotted arrays. One difficulty with array format is determining size location spots on array. In this paper we present a Bayesian approach to processing images by arrays that seeks posterior distributions over positions spots. This enables us estimate ratios their variances. Exact inference model specify intractable;...
ObjectiveThis project aims to identify the function of polarity protein complexes in formation primary cilia.We focus specifically on two apical complexes: Crumbs (Crb/Pals-1/PATJ) and PAR (Par3/Par6/ aPKC) complexes.In this study, we investigated role ciliogenesis.
Abstract In the spinal cord, adult central canal forms through a poorly-understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer. Here we show, in mouse, layer cells adjacent to midline Nestin (+) radial glia downregulate apical polarity proteins Crumbs2 (CRB2) aPKC delaminate step-wise manner; concomitantly, glial end-feet ratchet down, repeat this process. secrete factor promotes cell delamination. This activity is mimicked by...