Molecular Genetic Analysis of <i>Chd3</i> and Polytene Chromosome Region 76B-D in <i>Drosophila melanogaster</i>

Cooper, Monica T.; Conant, Alexander W.; Kennison, James A.

doi:10.1534/genetics.110.115121

Cited by 12 publications

(18 citation statements)

References 51 publications

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“…3L043 failed to complement the deficiencies Df(3L)Exel9061 and gyc76C KG03723ex33 . A bar marks a genomic region duplicated in the subset of the iso-1 strain used to generate the Berkeley Drosophila Genome Project (BDGP) genomic sequence, but unlikely to be duplicated in the mutagenized strain [ 57 ] ( S2 Fig ). (B) Domain structure of the Gyc76C protein, with an N-terminal, extracellular ANF receptor domain, a transmembrane (TM) domain, a putative phosphorylation site (phos), a kinase “dead” PTKc domain, a putative dimerization domain (dimer), and a C-terminal CYC domain.…”

Section: Resultsmentioning

confidence: 99%

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

Schleede

Blair

2015

PLoS Genet

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The developing crossveins of the wing of Drosophila melanogaster are specified by long-range BMP signaling and are especially sensitive to loss of extracellular modulators of BMP signaling such as the Chordin homolog Short gastrulation (Sog). However, the role of the extracellular matrix in BMP signaling and Sog activity in the crossveins has been poorly explored. Using a genetic mosaic screen for mutations that disrupt BMP signaling and posterior crossvein development, we identify Gyc76C, a member of the receptor guanylyl cyclase family that includes mammalian natriuretic peptide receptors. We show that Gyc76C and the soluble cGMP-dependent kinase Foraging, likely linked by cGMP, are necessary for normal refinement and maintenance of long-range BMP signaling in the posterior crossvein. This does not occur through cell-autonomous crosstalk between cGMP and BMP signal transduction, but likely through altered extracellular activity of Sog. We identify a novel pathway leading from Gyc76C to the organization of the wing extracellular matrix by matrix metalloproteinases, and show that both the extracellular matrix and BMP signaling effects are largely mediated by changes in the activity of matrix metalloproteinases. We discuss parallels and differences between this pathway and other examples of cGMP activity in both Drosophila melanogaster and mammalian cells and tissues.

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Section: Resultsmentioning

confidence: 99%

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

Schleede

Blair

2015

PLoS Genet

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“…We crossed the 968 male-sterile and barely fertile second-chromosome lines to three overlapping deficiencies that span the Adh region (∼2938 kb) [12] and identified 48 lines in which the hemizygous males were sterile and four lines in which the hemizygous flies were lethal. We crossed the 1428 male-sterile and barely-fertile third-chromosome lines to both Df(3L)kto2 (∼640 kb) [13] and Df(3L)th102 (∼315 kb) [14] and tested hemizygous males for fertility. Forty-one lines were identified in which the hemizygous males were sterile, and sixteen lines in which the hemizygous flies were lethal.…”

Section: Resultsmentioning

confidence: 99%

Anent the Genomics of Spermatogenesis in Drosophila melanogaster

2013

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An appreciable fraction of the Drosophila melanogaster genome is dedicated to male fertility. One approach to characterizing this subset of the genome is through the study of male-sterile mutations. We studied the relation between vital and male-fertility genes in three large autosomal regions that were saturated for lethal and male-sterile mutations. The majority of male-sterile mutations affect genes that are exclusively expressed in males. These genes are required only for male fertility, and several mutant alleles of each such gene were encountered. A few male-sterile mutations were alleles of vital genes that are expressed in both males and females. About one-fifth of the genes in Drosophila melanogaster show male-specific expression in adults. Although some earlier studies found a paucity of genes on the X chromosome showing male-biased expression, we did not find any significant differences between the X chromosome and the autosomes either in the relative frequencies of mutations to male sterility or in the frequencies of genes with male-specific expression in adults. Our results suggest that as much as 25% of the Drosophila genome may be dedicated to male fertility.

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“…Among these, a recent screen using Drosophila demonstrated that the best predictors of mutability are length and conservation of the protein (Cooper et al 2010). Based on the number of recessive lethal mutations identified after screening ∼3000 chromosomes, these investigators predicted that EMS generates one lethal mutation for every 73 evolutionarily conserved amino acids.…”

Section: Resultsmentioning

confidence: 99%

Restoration of Topoisomerase 2 Function by Complementation of Defective Monomers in Drosophila

et al. 2012

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Type II topoisomerases are essential ATP-dependent homodimeric enzymes required for transcription, replication, and chromosome segregation. These proteins alter DNA topology by generating transient enzyme-linked double-strand breaks for passage of one DNA strand through another. The central role of type II topoisomerases in DNA metabolism has made these enzymes targets for anticancer drugs. Here, we describe a genetic screen that generated novel alleles of Drosophila Topoisomerase 2 (Top2). Fifteen alleles were obtained, resulting from nonsense and missense mutations. Among these, 14 demonstrated recessive lethality, with one displaying temperature-sensitive lethality. Several newly generated missense alleles carry amino acid substitutions in conserved residues within the ATPase, Topoisomerase/Primase, and Winged helix domains, including four that encode proteins with alterations in residues associated with resistance to cancer chemotherapeutics. Animals lacking zygotic Top2 function can survive to pupation and display reduced cell division and altered polytene chromosome structure. Inter se crosses between six strains carrying Top2 missense alleles generated morphologically normal trans-heterozygous adults, which showed delayed development and were female sterile. Complementation occurred between alleles encoding Top2 proteins with amino acid substitutions in the same functional domain and between alleles encoding proteins with substitutions in different functional domains. Two complementing alleles encode proteins with amino acid substitutions associated with drug resistance. These observations suggest that dimerization of mutant Top2 monomers can restore enzymatic function. Our studies establish the first series of Top2 alleles in a multicellular organism. Future analyses of these alleles will enhance our knowledge about the contributions made by type II topoisomerases to development.

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Molecular Genetic Analysis of Chd3 and Polytene Chromosome Region 76B-D in Drosophila melanogaster

Cited by 12 publications

References 51 publications

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster

Anent the Genomics of Spermatogenesis in Drosophila melanogaster

Restoration of Topoisomerase 2 Function by Complementation of Defective Monomers in Drosophila

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