The vestigial locus of Drosophila melanogaster is involved in resistance to inhibitors of dTMP synthesis

Silber, Joël; Menn, Aline Le; Chevillard, Sylvie; Zider, Alain; Paumard, Solange

doi:10.1007/bf00280199

Cited by 6 publications

(4 citation statements)

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“…pairing-dependent regulation of gene expression as they have mutations in introns 3 and 2 respectively (each providing distinct regulatory sequences). Among these previous studies there was considerable variation observed in the degree of complementation (compare [ 3 , 31 ] with [ 13 ]). Thus, we decided to also examine vg allelic combinations including vg 1 and vg 83b27 for background dependence.…”

Section: Resultsmentioning

confidence: 99%

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

et al. 2017

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For a given gene, different mutations influence organismal phenotypes to varying degrees. However, the expressivity of these variants not only depends on the DNA lesion associated with the mutation, but also on factors including the genetic background and rearing environment. The degree to which these factors influence related alleles, genes, or pathways similarly, and whether similar developmental mechanisms underlie variation in the expressivity of a single allele across conditions and among alleles is poorly understood. Besides their fundamental biological significance, these questions have important implications for the interpretation of functional genetic analyses, for example, if these factors alter the ordering of allelic series or patterns of complementation. We examined the impact of genetic background and rearing environment for a series of mutations spanning the range of phenotypic effects for both the scalloped and vestigial genes, which influence wing development in Drosophila melanogaster. Genetic background and rearing environment influenced the phenotypic outcome of mutations, including intra-genic interactions, particularly for mutations of moderate expressivity. We examined whether cellular correlates (such as cell proliferation during development) of these phenotypic effects matched the observed phenotypic outcome. While cell proliferation decreased with mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the degree of background dependence. We discuss these findings and propose a phenomenological model to aid in understanding the biology of genes, and how this influences our interpretation of allelic effects in genetic analysis.

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Section: Resultsmentioning

confidence: 99%

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

et al. 2017

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“…This effect can be rescued by the addition of thymidine. 16 In addition, several enzymatic activities of the dTMP biosynthesis pathway, such as DHFR and thymidine kinase (TK), are perturbed in vg mutants. 15 Therefore, we conclude that vg could be a regulator of dTMP synthesis in the tissue where it is normally expressed.…”

Section: Introductionmentioning

confidence: 99%

The Drosophila wing differentiation factor Vestigial–Scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc

et al. 2003

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Links between genes involved in development, proliferation and apoptosis have been difficult to establish. In the Drosophila wing disc, the vestigial (vg) and the scalloped (sd) gene products dimerize to form a functional transcription factor. Ectopic expression of vg in other imaginal discs induces outgrowth and wing tissue specification. We investigated the role of the VG-SD dimer in proliferation and showed that vg antagonizes the effect of dacapo, the cyclin-cdk inhibitor. Moreover, ectopic vg drives cell cycle progression and in HeLa cultured cells, the VG-SD dimer induces cell proliferation per se. In Drosophila, ectopic vg induces expression of dE2F1 and its targets dRNR2 and string. In addition vg, but not dE2F1, interacts with and induces expression of dihydrofolate reductase (DHFR). Moreover, a decrease in VG or addition of aminopterin, a specific DHFR inhibitor, shift the dorso-ventral boundary cells of the disc to a cell death sensitive state that is correlated with reaper induction and DIAP1 downregulation. This indicates that vg in interaction with dE2F1 and DHFR is a critical player for both cell proliferation and cell survival in the presumptive wing margin area.

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“…pairing-dependent regulation of gene expression as they have mutations in introns 3 and 2 respectively (each providing distinct regulatory sequences). Indeed, among these previous studies there was considerable variation observed in the degree of complementation (compare [3,30] with [13]). Thus, we decided to also examine vg allelic combinations including vg 1 and vg 83b27 for background dependence.…”

Section: Resultsmentioning

confidence: 99%

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

Chandler

Chari

Kowalski

et al. 2017

Preprint

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42For a given gene, different mutations influence organismal phenotypes to varying 43 degrees. However, the expressivity of these variants not only depends on the DNA lesion 44 associated with the mutation, but also on factors including the genetic background and 45 rearing environment. The degree to which these factors influence related alleles, genes, or 46 pathways similarly, and whether similar developmental mechanisms underlie variation in the 47 expressivity of a single allele across conditions and variation across alleles is poorly 48 understood. Besides their fundamental biological significance, these questions have 49 important implications for the interpretation of functional genetic analyses, for example, if 50 these factors alter the ordering of allelic series or patterns of complementation. We 51 examined the impact of genetic background and rearing environment for a series of 52 mutations spanning the range of phenotypic effects for both the scalloped and vestigial 53 genes, which influence wing development in Drosophila melanogaster. Genetic background 54 and rearing environment influenced the phenotypic outcome of mutations, including intra-55 genic interactions, particularly for mutations of moderate expressivity. We examined whether 56 cellular correlates (such as cell proliferation during development) of these phenotypic effects 57 matched the observed phenotypic outcome. While cell proliferation decreased with 58 mutations of increasingly severe effects, surprisingly it did not co-vary strongly with the 59 degree of background dependence. We discuss these findings and propose a 60 phenomenological model to aid in understanding the biology of genes, and how this 61 influences our interpretation of allelic effects in genetic analysis. 62 63 Author Summary 64 Different mutations in a gene, or in genes with related functions, can have effects of 65 varying severity. Studying sets of mutations and analyzing how they interact are essential 66 components of a geneticist's toolkit. However, the effects caused by a mutation depend not 67 only on the mutation itself, but on additional genetic variation throughout an organism's 68 genome and on the environment that organism has experienced. Therefore, identifying how 69 the genomic and environmental context alter the expression of mutations is critical for 70 making reliable inferences about how genes function. Yet studies on this context 71 dependence have largely been limited to single mutations in single genes. We examined 72 how the genomic and environmental context influence the expression of multiple mutations 73 in two related genes affecting the fruit fly wing. Our results show that the genetic and 74 3 environmental context generally affect the expression of related mutations in similar ways. 75 However, the interactions between two different mutations in a single gene sometimes 76 depended strongly on context. In addition, cell proliferation in the developing wing and adult 77 wing size were not affected by the genetic and environmental context...

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The vestigial locus of Drosophila melanogaster is involved in resistance to inhibitors of dTMP synthesis

Cited by 6 publications

References 13 publications

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

The Drosophila wing differentiation factor Vestigial–Scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc

How well do you know your mutation? Complex effects of genetic background on expressivity, complementation, and ordering of allelic effects

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