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Alexander Davies Caroline Formstone Ivor Mason Julian Lewis 《Developmental dynamics》2005,233(3):998-1005
Hair cells of the vertebrate inner ear are directional mechanosensors: they have a polarity, defined by a vector in the plane of the sensory epithelium. It has been suggested that this polarity might be controlled by genes homologous to those that control planar cell polarity (PCP) in Drosophila, and vertebrate homologues of the Drosophila PCP genes Van Gogh/strabismus and flamingo/starry night are indeed essential for normal hair cell PCP. The underlying molecular mechanism is unclear, however. Although the PCP protein Flamingo shows a polarized intracellular distribution in the fly, it is unknown whether this is necessary for its function. Here, we describe the expression pattern of a flamingo homologue, c-flamingo-1 (c-fmi-1), in the developing chick ear and show that its protein product, like that of flamingo in the fly, has a polarized distribution in each hair cell, defining an axis that corresponds to the structural PCP axis. This conservation between fly and vertebrate suggests that the polarized protein localization is functionally important. In the basilar papilla, the same localization is seen in supporting cells also, suggesting that supporting cells are cryptically polarized, despite having no overt structural polarity; they may thus participate in PCP signal transmission across the sensory patch. 相似文献
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Formstone CJ; Hallam PJ; Tuddenham EG; Voke J; Layton M; Nicolaides K; Hann IM; Cooper DN 《Blood》1996,87(9):3731-3737
Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency. This pregnancy proceeded to a full-term delivery without thrombotic complications. Molecular genetic analysis of the PROC and PROS gene segregating in the family then yielded one PROC gene lesion in the father and two PROS gene lesions, one in each parent. These lesions were shown to segregate with the respective deficiency states through the family pedigree. Analysis of DNA from paraffin-embedded liver tissue taken from the deceased child showed the presence of both PROS mutations, as well as the PROC mutation. Genotypic analysis of the second child showed a PROC mutation, but neither PROS mutation consistent with its possession of normal protein S levels and a low/borderline protein C level. Antenatal diagnosis was then performed in a third pregnancy by direct mutation detection. However, although the fetus carried only the paternal PROS and PROC gene lesions, the child developed renal thrombosis in utero. It may be that a further genetic lesion at a third locus still remains to be defined. Alternatively, the intrauterine development of thrombosis in this infant could have been caused, at least in part by a transplacental thrombotic stimulus arising in the protein S-deficient maternal circulation. This analysis may, therefore, serve as a warning against extrapolating too readily from genotype to phenotype in families with a complex thrombotic disorder. 相似文献
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Veronica McCabe Emma J. Formstone Laura P. ONeill Bryan M. Turner Neil Brockdorff 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(13):7155-7160
The Xist gene is expressed exclusively from the inactive X chromosome and plays a central role in regulating X chromosome inactivation. Here we describe experiments aimed at defining the extent of the active chromatin domain of the expressed Xist allele. By using an allele-specific general DNaseI sensitivity assay we show that there is preferential digestion of the expressed allele at sites within the transcribed locus but not in flanking sites located up to 70 kb 5'. A putative proximal boundary for the Xist domain is located within 10 kb upstream of promoter P1. Chromatin in the expressed domain was found to be acetylated at H4 in XX somatic cells but also in XY cells, where Xist is never expressed. A single clear exception to this was the Xist promoter, which is acetylated only in XX cells. These observations concur with the view that H4 acetylation may not be a general marker of active chromatin domains and further support data implicating local promoter acetylation as being of primary functional significance in vivo. 相似文献
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Cloning of Tabby, the murine homolog of the human EDA gene: evidence for a membrane-associated protein with a short collagenous domain 总被引:7,自引:4,他引:7
Ferguson BM; Brockdorff N; Formstone E; Ngyuen T; Kronmiller JE; Zonana J 《Human molecular genetics》1997,6(9):1589-1594
X-Linked hypohidrotic ectodermal dysplasia (XLHED) is a human congenital
disorder resulting in abnormal tooth, hair and sweat gland development. A
candidate gene for the disorder has been cloned, but the function and full
size of its putative protein product is unclear. We have identified a
candidate cDNA for the mouse Tabby gene (Ta), which, based on phenotype and
syntenic mapping, is postulated to represent the analogous murine disorder.
Mutations have been identified in three different Ta alleles and Northern
analysis indicates that the gene is expressed at increasing levels during
embryogenesis (11-17 days p.c.), the period when affected structures
develop. The putative protein product encoded by exon 1 is highly
homologous (87% identical) to the predicted EDA protein product (135 amino
acids), including the presence of a single transmembrane domain. However,
the murine cDNA also encodes an additional 246 amino acids, which contains
a short collagenous domain (Gly-X-Y)19. This predicted structure is similar
to a number of membrane-associated proteins with either single or multiple
collagenous domains in their extracellular C-terminal regions. Since
mutations can only be identified in 10-15% of families with XLHED, it is
likely that additional homologous exons exist for the human EDA gene.
Hybridization of YACs from the EDA region with the Ta cDNA support this
hypothesis. The predicted extracellular collagenous domain of this membrane
protein may play a key role in epithelial-mesenchymal interactions, defects
of which are thought to underlie the Ta/XLHED phenotype.
相似文献
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A M Taylor P A Lowe M Stacey J Thick L Campbell D Beatty P Biggs C J Formstone 《Leukemia》1992,6(9):961-966
Ataxia telangiectasia is a rare inherited and progressive neurological disorder in which patients show an unusual predisposition to T-cell leukaemia. We report here observations on a patient with a large cytogenetically abnormal clone showing a single t(X;14)(q28;q11) translocation which conferred a proliferative advantage on the cells. The further evolution of this clone to cytogenetically more complex clones of lymphocytes was seen in the patient. She subsequently developed a rapidly progressing T-cell leukaemia, with a CD4+CD8+ T-cell phenotype, about five years after the first appearance of additional chromosome translocations in the clone cells. 相似文献
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Gandrille S Borgel D Sala N Espinosa-Parrilla Y Simmonds R Rezende S Lind B Mannhalter C Pabinger I Reitsma PH Formstone C Cooper DN Saito H Suzuki K Bernardi F Aiach M;Plasma Coagulation Inhibitors Subcommittee of the Scientific Standardization Committee of the International Society on Thrombosis Haemostasis 《Thrombosis and haemostasis》2000,84(5):918
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