Defective gap-junctional communication associated with imaginal disc overgrowth and degeneration caused by mutations of the dco gene in Drosophila

Jursnich, Victoria A.; Fraser, Scott E.; Held, Lewis I.; Ryerse, Jan S.; Bryant, Peter J.

doi:10.1016/0012-1606(90)90090-6

Cited by 60 publications

(30 citation statements)

References 38 publications

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“…Most cells in late 3rd instar wing discs are stalled in G2 (Neufeld et al, 1998). The observed cell division clustering in the wing disc suggests that the decision to start M-phase might be regulated at some level between neighboring cells, perhaps through gap junction communication (Bryant and Fraser, 1988;Jursnich et al, 1990). Indeed, a proper appreciation of spatiotemporal clustering might be required to properly interpret some experiments that rely on clonal analysis (Griffin et al, 2009).…”

Section: Spatiotemporal Clustering Of Cell Divisionsmentioning

confidence: 99%

A high-throughput template for optimizingDrosophilaorgan culture with response-surface methods

2013

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Section: Spatiotemporal Clustering Of Cell Divisionsmentioning

confidence: 99%

A high-throughput template for optimizingDrosophilaorgan culture with response-surface methods

2013

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“…The following missense mutations were identified: I29T (atc3aac); A36G (gcc3ggc); L39Q (ctg3cag; detected in 5 of the 9 cases sequenced); L49Q (ctg3cag; detected three times); E52K (gag3aag); G64A (ggg3gcg); G72A (gga3gca); A73V (gct3gtt; detected twice); N78T (aac3acc); and S101R (agc3agg; detected twice). One mutation to a stop codon was found (E74*; cag3tag), affecting a residue homologous to the one mutated in the dco 3 Drosophila mutant, which was the only dco allele found to give a robust overgrowth phenotype (13,14). The A36G and E52K mutations occur at residues known to participate in ATP binding.…”

Section: Somaticmentioning

confidence: 99%

“…This gene encodes casein kinase 1-⑀ (CKI⑀), a serinethreonine kinase whose overexpression mimics Wnt signaling by stabilizing ␤-catenin, thereby increasing expression of ␤-catenindependent genes. CKI⑀ is homologous to the product of the Drosophila TSG dco (discs overgrown) in which some allelic combinations result in overgrowth phenotypes (13,14). CKI⑀ is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself (15,16).…”

Section: Introductionmentioning

confidence: 99%

Somatic Mutations and Altered Expression of the Candidate Tumor Suppressors CSNK1ε , DLG1 , and EDD/hHYD in Mammary Ductal Carcinoma

Fuja

Lin²,

Osann³

et al. 2004

Cancer Research

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120

111

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We report somatic mutations in three genes (CSNK1⑀, encoding the Ser/Thr kinase casein kinase I ⑀; DLG1, encoding a membrane-associated putative scaffolding protein; and EDD/hHYD, encoding a progestin induced putative ubiquitin-protein ligase) in mammary ductal carcinoma. These genes were suspected of playing a role in cancer because loss-offunction mutations in their Drosophila homologues cause excess tissue growth. Using DNA from 82 laser-microdissected tumor samples, followed by microsatellite analysis, denaturing HPLC and direct sequencing, we found multiple somatic point mutations in all three genes, and these mutations showed significant association with loss of heterozygosity of closely linked polymorphic microsatellite markers. For CSNK1⑀ and DLG1, most of the mutations affected highly conserved residues, some were found repetitively in different patients, and no synonymous mutations were found, indicating that the observed mutations were selected in tumors and may be functionally significant. Immunohistochemical reactivity of each protein was reduced in poorly differentiated tumors, and there was a positive association between altered protein reactivity, loss of heterozygosity, and somatic mutations. There was a statistically significant association of hDlg staining with p53 and Ki67 reactivity, whereas CSK1⑀ and EDD/hHYD staining levels were associated with progesterone receptor status. The results provide strong indications for a role of all three genes in mammary ductal carcinoma. They also justify additional studies of the functional significance of the changes, as well as a search for additional changes in these and other genes identified from studies on model systems.

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“…Jursnich et al, 1990 domain structure as Notch, with amino acid identities in the range of 50-70% (Fig. 2).…”

Section: Tsgs Functioning In the Embryomentioning

confidence: 99%

Drosophila in cancer research: the first fifty tumor suppressor genes

Watson

Justice

Bryant

1994

Journal of Cell Science

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110

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SUMMARYIn Drosophila, over 50 genes have been identified in which loss-of-function mutations lead to excess cell proliferation in the embryo, in the central nervous system, imaginal discs or hematopoietic organs of the larva, or in the adult gonads. Twenty-two of these genes have been cloned and characterized at the molecular level, and nine of them show clear homology to mammalian genes. Most of these mammalian genes had not been previously implicated in cell proliferation control. Overgrowth in some of the mutants involves conversion to a cell type that, in normal development, shows more cell proliferation than the original cell type. Thus the neurogenic mutants, including Notch, show conversion of epidermal cells to neuroblasts, leading to the 'neurogenic' phenotype of excess nervous tissue. The ovarian tumor mutants show conversion of the female germ line to a cell type resembling the male germ line, which undergoes more proliferation than the female germ line. Mutations of the fa t locus cause hyperplastic overgrowth of imaginal discs, in which the epithelial structure is largely intact. The predicted fat protein product is a giant relative of cadherins, supporting indica tions from human cancer that cadherins play an important role in tumor suppression. Mutations in the lethal(2)giant larvae and lethal(l)discs large genes cause neoplastic over growth of imaginal discs as well as the larval brain. The dig gene encodes a membrane-associated guanylate kinase homolog that is localized at septate junctions between epithelial cells. This protein is a member of a family of homologs that also includes two proteins found at mammalian tight junctions (ZO-1 and ZO-2) and a protein found at mammalian synaptic junctions (PSD-95/SAP90). Genes in which mutations cause blood cell overproduction include aberrant immune response-8, which encodes the RpS6 ribosomal protein and hopscotch, which encodes a putative non-receptor protein tyrosine kinase. The gene products identified by ovarian tumor mutants do not show clear amino acid sequence homology to known proteins. Drosophila provides an opportunity to rapidly identify and characterize tumor suppressor genes, many of which have mammalian homologs that might also be involved in cell proliferation control and tumor suppression.

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Defective gap-junctional communication associated with imaginal disc overgrowth and degeneration caused by mutations of the dco gene in Drosophila

Cited by 60 publications

References 38 publications

A high-throughput template for optimizingDrosophilaorgan culture with response-surface methods

A high-throughput template for optimizingDrosophilaorgan culture with response-surface methods

Somatic Mutations and Altered Expression of the Candidate Tumor Suppressors CSNK1ε , DLG1 , and EDD/hHYD in Mammary Ductal Carcinoma

Drosophila in cancer research: the first fifty tumor suppressor genes

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