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PubMedDate not supplied

[The influence of gamma-irradiation in low doses on the rate of dominant lethal mutations in drosophila melanogaster].

The dose-rate effect of acute and chronic irradiation in the dose of 0.2 Gy in Drosophila melanogaster repair (mei-41, mus209 [Russian character: see text] mus309) and free radicals detoxication (sod) mutant strains was investigated. Was shown the lack of dose rate effect on the rate of dominant lethal mutations in mei-41, mus209 and sod. However in mus309, that has defect in the main Drosophila pathway of the DNA double strand breack repair, the increase of the mutation rate after chronic irradiation was observed (inverse dose-rate effect). The obtained results suggest the main role of DNA double strand breack repair in dose-rate effect formation in Drosophila.

Animals↗
PubMed1995

A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain.

Inactivation of the tumour suppressor gene lethal(2) giant larvae (D-lgl) of Drosophila leads to malignant transformation of the presumptive adult optic centers in the larval brain and tumours of the imaginal discs. These malignancies result from the disorganization of a cytoskeletal network in which the D-LGL protein participates. Here we describe the isolation of a cDNA encoding the human homologue to the D-lgl gene designated as hugl. The hugl cDNA detects a locus spanning at least 25 kilobases (kb) in human chromosome band 17p11.2-12, which is centromeric to the p53 gene and recognizes a 4.5 kb RNA transcript. The hugl gene is expressed in brain, kidney and muscle but is barely seen in heart and placenta. Sequence analysis of the hugl cDNA demonstrates a long open reading frame, which has the potential to encode a protein of 1057 amino acids with a predicted molecular weight of 115 kDaltons (kD). To further substantiate and identify the HUGL protein, we have prepared polyclonal rabbit antibodies against synthetic peptides corresponding to the amino and carboxyl termini of the conceptual translation product of the hugl gene. The affinity-purified anti-HUGL antibodies recognize a single protein with an apparent molecular weight of approximately 115 kD. Similar to the Drosophila protein, HUGL is part of a cytoskeletal network and, is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates HUGL at serine residues.

Amino Acid Sequence↗
PubMed1995

A POU homeo domain protein related to dPOU-19/pdm-1 binds to the regulatory DNA necessary for vital expression of the Drosophila choline acetyltransferase gene.

Expression of the choline acetyltransferase (ChAT) gene in Drosophila melanogaster is responsible for production of the neurotransmitter acetylcholine and is necessary for viability. In previous studies, we have shown that the regulatory region for normal ChAT expression is large and composed of multiple regulatory elements (Kitamoto et al., 1992; Kitamoto and Salvaterra, 1993). In this study, using various lengths of 5' flanking DNA fused to wild type ChAT cDNA, we have defined a 0.3 kilobase (kb) region of the cis-regulatory DNA, which is essential for restoring viability of Cha lethal mutants. DNase I footprinting analysis of this 0.3 kb DNA revealed a protected 22 bp sequence that contains an octamer-like motif (ATTCAAAT) with one base difference from the consensus octamer motif (ATGCAAAT). Electrophoretic mobility shift assays and Southwestern blot analysis confirmed the presence of specific binding factor(s) for the 22 bp sequence in embryo nuclear extracts, and competition studies established the importance of the octamer-like motif for high-affinity binding. Using the 22-mer as a probe, we have isolated a cDNA clone encoding the Drosophila POU homeo domain protein, dPOU-19/pdm-1, whose target genes and specific binding sequences have not been identified. We propose that vital expression of the Drosophila ChAT gene is regulated by a member of the dPOU-19/pdm-1 putative transcription factor family.

Animals↗
PubMed1995

Can clues to the molecular defects in chronic myelogenous leukemia come from genetic studies on the Abelson tyrosine kinase in fruit flies?

Translocations affecting the structure of the c-abl proto-oncogene are involved in the development or progression of chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). Leukemic cells from patients with CML show alterations in adhesive properties that may play a part in the pathology of these diseases. Mutations in the Drosophila Abl homolog are lethal and indicate that Abl may mediate processes involving differential cell adhesion. These observations suggest that Abl may regulate similar adhesive processes in human beings and Drosophila. Genetic analysis of Abl function in Drosophila has identified novel proteins that function in Abl-related processes. Analysis of the functions of these new molecules may provide insight into mechanisms by which oncogenic abl proteins participate in the etiology of CML and ALL.

Animals↗
PubMed1993

Evolution and aggregulates: role of the Polycomb-group genes of Drosophila.

The Polycomb-group (Pc-G) genes of Drosophila melanogaster are responsible for fixation of the repressed state for other selector genes, mostly homeotic but not exclusively. Different arguments suggest that they work cooperatively by specific recognition and structural modification of their targets. Their pleiotropic mutant phenotypes are strikingly similar to morphological traits used to classify Dipteran groups. I propose that the products of Pc-G genes can form a combinatorial multimeric regulatory system (the Aggregulates of F. Jacob) and that stable variations in the composition of this system have played an important role in Dipteran evolution.

Animals↗
PubMedDate not supplied

[The production of mutants in the genes of microtubule proteins].

Data on the methods for obtaining microtubule mutants with the aim of studying the structural and functional properties of the microtubules and their components are generalized in the review. An analysis of mechanisms providing resistance of plant and animal cells to the compounds with antimicrotubular activity is made.

Animals↗
PubMed1993

[Mutagenic effect of pindone on D. melanogaster].

A commercial grade Pindone was tested for the induction of genetic damage in male germ cells of Drosophila melanogaster by adult ingestion. Adults were starved for 4 days and then fed pindone at a concentration of 1 mM in ethyl alcohol 15% containing sucrose 5%. Pindone was found to increase the frequency of sex chromosome loss. Results were significant at the 1% level (Kastenbaum-Bowman test). However no significant results were obtained by the sex linked recessive lethal assay.

Animals↗
PubMed1993

Characterization of lethal alleles of D-elg, an ets proto-oncogene related gene with multiple functions in Drosophila development.

We have used genetic complementation rescue to identify two lethal alleles of D-elg, an ets proto-oncogene related gene of Drosophila. Animals that are hemizygous or trans-heterozygous for the alleles die as pharate adults, demonstrating normal gene function is required to complete Drosophila development. Females trans-heterozygous for the 1(3)902 lethal allele and the previously characterized tne female sterile allele produce embryos with abdominal segmentation defects. This finding implicates a role for the D-elg gene in anterior-posterior patterning. The cloning and sequencing of the lethal alleles identified molecular mutations that may result in ELG protein truncation, altered ELG protein interactions, or defective D-elg mRNA splicing.

Alleles↗
PubMed1995

Neural induction and neurogenesis in amphibian embryos.

Neural induction has long been known as the process by which the ectoderm of vertebrate embryos initiates neural development. During this inductive interaction, a region of the embryo called the organizer is a source of inducing signals that directs ectoderm away from an epidermal into a neural fate, thereby forming the neural plate and tube. In this review, we will discuss recent progress in characterizing two molecules in Xenopus embryos, noggin and follistatin, which appear to have many of the properties expected of neural inducers produced by the organizer. In addition, we will discuss progress that has been made in characterizing Xenopus homologs of the neurogenic and proneural genes that control the decision between a neural and epidermal fate in the Drosophila embryos. A model is presented in which these genes act downstream of neural induction in vertebrates to control the generation of neural precursor cells during neurogenesis.

Activins↗
PubMed1996

Probes of chromatin accessibility in the Drosophila bithorax complex respond differently to Polycomb-mediated repression.

The Polycomb group (PcG) of genes are required for maintenance of the repressed state of the homeotic genes in Drosophila. There are similarities between the PcG repression and mating-type silencing in yeast or heterochromatic position effect in Drosophila, which suggest that PcG repression may involve a highly compacted chromatin structure. To test for such a structure, heterologous DNA- binding proteins were used as probes for DNA accessibility in Drosophila embryos. Binding sites for the yeast transcriptional activator GAL4 and for bacteriophage T7 RNA polymerase were inserted into the bithorax (bx) regulatory region of the endogenous Ultrabithorax (Ubx) gene, which is regulated by the PcG. Ubiquitously expressed GAL4 protein directs transcription through its binding sites only in the posterior segments where the bx region is active. The block to GAL4 activation in the more anterior segments is dependent on Polycomb (Pc) function. In contrast, T7 RNA polymerase can transcribe from its target promoter in all segments of the embryo. Thus, Pc-mediated repression blocks activated polymerase II transcription, but does not simply exclude all proteins.

Animals↗
PubMed1996

Developmental timing and tissue specificity of heterochromatin-mediated silencing.

Heterochromatic position-effect variegation (PEV) describes the mosaic phenotype of a euchromatic gene placed next to heterochromatin. Heterochromatin-mediated silencing has been studied extensively in Drosophila, but the lack of a ubiquitous reporter gene detectable at any stage has prevented a direct developmental characterization of this phenomenon. Current models attribute variegation to the establishment of a heritable silent state in a subset of the cells and invoke differences in the timing of silencing to explain differences in the patch size of various mosaic patterns. In order to follow the course of heterochromatic silencing directly, we have generated Drosophila lines variegating for a lacZ reporter that can be induced in virtually all cells at any developmental stage. Our data indicate that silencing begins in embryogenesis and persists in both somatic and germline lineages. A heterogeneity in the extent of silencing is also revealed; silencing is suppressed in differentiated tissues but remains widespread in larval imaginal discs containing precursor cells for adult structures. Using eye development as an example, we propose that the mosaic phenotype is determined during differentiation by a variegated relaxation in heterochromatic silencing. Though unpredicted by prevailing models, this mechanism is evident in other analogous systems.

Animals↗
PubMed1996

[Differential characteristics of the temperature-sensitive period of the lawcp1 mutation on the basis of macrochaetae overexpression in Drosophila].

Temperature-sensitive periods (TSPs) of lawcpl mutations were studied via the frequencies of arising of extras macrochaetae for each macrochaetae type separately. TSPs for the formation of extras macrochaetae of original classes were unevenly distributed within larval instars II and III. It was found that macrochaetae of different types differed from one another in their temperature sensitivity. The TSP of development of macrochaetae belonging to new ectopic classes was multiphase, with the first phase at larval instar II, and the second phase, at the prepupal to early pupal stage. It is assumed that in Drosophila, the products of the lawc gene participate, along with other genes, in the development of the nervous system through regulation of ac-sc expression, both in proneural clusters and outside them.

Alleles↗
PubMed1996

Drosophila differentiation genes instrumental in tumor suppression.

Tumor suppressor genes of Drosophila are developmental genes which, in the homozygously mutated state, induce in one step malignant or benign neoplastic transformation of specific cell types. They act early in development and by this set the stage for cell specific differentiation of imaginal discs, adult optic neuroblasts, blood and gonial cells. The structure, expression and possible function of the following four tumor suppressor genes are discussed: tumorous imaginal disc, lethal (3) malignant brain tumor, lethal (3) malignant blood neoplasm-1 and benign (2) gonial cell neoplasm.

Animals↗