Drosophila purine auxotrophy: New alleles ofadenosine2 exhibiting a complex visible phenotype

Tiong, Stanley; Keizer, C.; Nash, David R.; Bleskan, John; Patterson, David

doi:10.1007/bf00554168

Cited by 23 publications

(18 citation statements)

References 18 publications

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“…Pigmentation in these mutants is normal, however. Additionally, de novo pyrimidine mutants in Drosophila often possess defects in wing formation (Rawls and Fristrom, 1975;Falk, 1976), whereas mutants in de novo purine biosynthesis have defects in eye color (Tiong et al, 1989). These studies, when combined with our results, support a model in which de novo purine biosynthesis and de novo pyrimidine biosynthesis play important but tissue-specific roles during animal development.…”

Section: Research Articlesupporting

confidence: 82%

“…Perhaps the most well-studied model for the function of the de novo purine synthesis pathway during development comes from work in Drosophila, in which mutations in prat (ppat) (Clark, 1994), ade2 (pfas) (Henikoff et al, 1986b;Johnstone et al, 1985), ade3 (gart) (Henikoff et al, 1986a;Johnstone et al, 1985) and ade5 (paics) (O'Donnell et al, 2000) have been identified, as well as mutations in the GTP pathway components IMPDH (raspberry) and GMP synthase (burgundy) (Johnstone et al, 1985;Long et al, 2006). Each of these de novo pathway mutants shows a subset of developmental defects that have collectively been termed the 'purine syndrome' phenotype (Tiong et al, 1989). Purine syndrome defects include a reduction in the red pteridine-derived eye pigments, bristle and leg malformations, small wings, and pupal lethality (Tiong et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…Each of these de novo pathway mutants shows a subset of developmental defects that have collectively been termed the 'purine syndrome' phenotype (Tiong et al, 1989). Purine syndrome defects include a reduction in the red pteridine-derived eye pigments, bristle and leg malformations, small wings, and pupal lethality (Tiong et al, 1989). Additionally, IMPDH and GMP synthase mutants possess defects in R-cell axon pathfinding (Long et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Zebrafish mutations ingartandpaicsidentify crucial roles for de novo purine synthesis in vertebrate pigmentation and ocular development

Uribe

Yieh

et al. 2009

Development

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Although purines and purinergic signaling are crucial for numerous biochemical and cellular processes, their functions during vertebrate embryonic development have not been well characterized. We analyze two recessive zebrafish mutations that affect de novo purine synthesis, gart and paics. gart encodes phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase, a trifunctional enzyme that catalyzes steps 2, 3 and 5 of inosine monophosphate (IMP) synthesis. paics encodes phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase, a bifunctional enzyme that catalyzes steps 6 and 7 of this process. Zygotic gart and paics mutants have pigmentation defects in which xanthophore and iridophore pigmentation is almost completely absent, and melanin-derived pigmentation is significantly decreased, even though pigment cells are present in normal amounts and distributions. Zygotic gart and paics mutants are also microphthalmic, resulting from defects in cell cycle exit of proliferative retinoblasts within the developing eye. Maternal-zygotic and maternal-effect mutants demonstrate a crucial requirement for maternally derived gart and paics; these mutants show more severe developmental defects than their zygotic counterparts. Pigmentation and eye growth phenotypes in zygotic gart and paics mutants can be ascribed to separable biosynthetic pathways: pigmentation defects and microphthalmia result from deficiencies in a GTP synthesis pathway and an ATP synthesis pathway, respectively. In the absence of ATP pathway activity, S phase of proliferative retinoblasts is prolonged and cell cycle exit is compromised, which results in microphthalmia. These results demonstrate crucial maternal and zygotic requirements for de novo purine synthesis during vertebrate embryonic development, and identify independent functions for ATP and GTP pathways in mediating eye growth and pigmentation, respectively.

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Section: Research Articlesupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Zebrafish mutations ingartandpaicsidentify crucial roles for de novo purine synthesis in vertebrate pigmentation and ocular development

Uribe

Yieh

et al. 2009

Development

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“…To ask whether the lethal phenotype caused by double RNAi for Prat and Prat2 has a similar phenotype as that caused by the mutations of single-copy genes that act downstream in the de novo purine pathway, we characterized the pupal lethal phenotype of ade2 by crossing two EMS-induced ade2 lethal alleles (ade2 3 and ade2 4 ) (Tiong et al 1989). We found that 8% of ade2 3 /ade2 4 pupae arrested at the P2 stage with defects in eversion of the anterior spiracle and failure of gas bubble movement (Table 5 and Figure 4C), which is very similar to the earliest arrested prepupae caused by double RNAi for Prat and Prat2 ( Figure 4B).…”

Section: A6mentioning

confidence: 99%

The Purine Synthesis Gene Prat2 Is Required for Drosophila Metamorphosis, as Revealed by Inverted-Repeat-Mediated RNA Interference

Clark

2006

Genetics

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PRAT (phosphoribosylamidotransferase; E.C. 2.4.2.14) catalyzes the first reaction in de novo purine nucleotide biosynthesis. In Drosophila melanogaster, the Prat and Prat2 genes are both highly conserved with PRAT sequences from prokaryotes and eukaryotes. However, Prat2 organization and expression during development is different from Prat. We used RNA interference (RNAi) to knock down expression of both Prat and Prat2 to investigate their functions. Using the GAL4-UAS system, Prat RNAi driven by Act5c-GAL4 or tubP-GAL4 causes variable pupal lethality (48-100%) and 50% female sterility, depending on the transgenic strains and drivers used. This observation agrees with the phenotype previously observed for Prat EMSinduced mutations. Prat2 RNAi driven by Act5C-GAL4 or tubP-GAL4 also results in variable pupal lethality (61-93%) with the different transgenic strains, showing that Prat2 is essential for fly development. However, Prat2 RNAi-induced arrested pupae have a head eversion defect reminiscent of the ''cryptocephal'' phenotype, whereas Prat RNAi-induced arrested pupae die later as pharate adults. We conclude that Prat2 is required during the prepupal stage while Prat is more important for the pupal stage. In addition, Prat and Prat2 double RNAi results in more severe pupal lethal phenotypes, suggesting that Prat and Prat2 have partially additive functions during Drosophila metamorphosis.

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“…PAICS is highly conserved in higher eukaryotes, and mutations in PAICS can result in developmental defects and in some cases embryonic lethality (Tiong et al 1989;Ng et al 2009). Additionally, because cancer cells rely heavily on the de novo purine biosynthesis pathway while normal cells preferentially utilize salvage pathways (Li et al 2007), PAICS has emerged as a potential target for anticancer drugs.…”

Section: Weeks 4-7: Using Yeast To Study Enzyme Defectsmentioning

confidence: 99%

An Integrated Biochemistry and Genetics Outreach Program Designed for Elementary School Students

Ross

Lee²,

Radebaugh

et al. 2012

Genetics

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Exposure to genetic and biochemical experiments typically occurs late in one's academic career. By the time students have the opportunity to select specialized courses in these areas, many have already developed negative attitudes toward the sciences. Given little or no direct experience with the fields of genetics and biochemistry, it is likely that many young people rule these out as potential areas of study or career path. To address this problem, we developed a 7-week (1 hr/week) hands-on course to introduce fifth grade students to basic concepts in genetics and biochemistry. These young students performed a series of investigations (ranging from examining phenotypic variation, in vitro enzymatic assays, and yeast genetic experiments) to explore scientific reasoning through direct experimentation. Despite the challenging material, the vast majority of students successfully completed each experiment, and most students reported that the experience increased their interest in science. Additionally, the experiments within the 7-week program are easily performed by instructors with basic skills in biological sciences. As such, this program can be implemented by others motivated to achieve a broader impact by increasing the accessibility of their university and communicating to a young audience a positive impression of the sciences and the potential for science as a career.

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Drosophila purine auxotrophy: New alleles ofadenosine2 exhibiting a complex visible phenotype

Cited by 23 publications

References 18 publications

Zebrafish mutations ingartandpaicsidentify crucial roles for de novo purine synthesis in vertebrate pigmentation and ocular development

Zebrafish mutations ingartandpaicsidentify crucial roles for de novo purine synthesis in vertebrate pigmentation and ocular development

The Purine Synthesis Gene Prat2 Is Required for Drosophila Metamorphosis, as Revealed by Inverted-Repeat-Mediated RNA Interference

An Integrated Biochemistry and Genetics Outreach Program Designed for Elementary School Students

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