transforming-growth-factor-alpha and Infertility--Female

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During

Topics: Animals; Body Patterning; DNA-Binding Proteins; Drosophila melanogaster; Drosophila Proteins; Female; Gene Expression Regulation, Developmental; Infertility, Female; Introns; RNA Splicing; Spliceosomes; Transforming Growth Factor alpha

Localization of specific mRNAs to distinct sites within the Drosophila oocyte is an early and key step in establishing the anterior-posterior and dorsal-ventral axes. We describe a new function for the RNA helicase encoded by the "posterior" group gene vasa (vas) in control of localization of the mRNA encoded by the "dorsal-ventral" patterning gene gurken (grk). Two new ethyl methane sulfonate-induced, female sterile alleles of vas have been isolated. In these mutants grk mRNA fails to become localized properly and GRK protein is barely detectable. Surprisingly fs(1)K10, a recessive female sterile mutation that results in mislocalization of GRK mRNA to the anterior end of the oocyte, is epistatic to these vas alleles. This result demonstrates that GRK protein levels sufficient to dorsalize the egg chamber can accumulate in vas mutants, if fs(1)K10 is also mutant. Taken together these results suggest that regulation of GRK mRNA localization normally occurs, directly or indirectly, through the VAS RNA-dependent RNA helicase and may suggest that accumulation of GRK protein normally depends on GRK mRNA localization.

Topics: Alleles; Animals; Body Patterning; Cell Compartmentation; DEAD-box RNA Helicases; Drosophila; Drosophila Proteins; Epistasis, Genetic; Female; Genes, Insect; Genetic Complementation Test; Infertility, Female; Insect Proteins; Mutation; Oocytes; Oogenesis; Phenotype; RNA Helicases; RNA Nucleotidyltransferases; RNA, Messenger; Transforming Growth Factor alpha; Transforming Growth Factors

Mice lacking p27(Kip1) have been created by gene targeting in embryonic stem cells. These mice are larger than the control animals, with thymus, pituitary, and adrenal glands and gonadal organs exhibiting striking enlargement. CDK2 activity is elevated about 10-fold in p27(-/-) thymocytes. Development of ovarian follicles seems to be impaired, resulting in female sterility. Similar to mice with the Rb mutation, the p27(-/-) mice often develop pituitary tumors spontaneously. The retinas of the mutant mice show a disturbed organization of the normal cellular layer pattern. These findings indicate that p27(Kip1) acts to regulate the growth of a variety of cells. Unexpectedly, the cell cycle arrest mediated by TGFbeta, rapamycin, or contact inhibition remained intact in p27(-/-) cells, suggesting that p27(Kip1) is not required in these pathways.

Topics: Animals; Base Sequence; Body Constitution; Cell Cycle; Cell Cycle Proteins; Cell Division; Cyclin-Dependent Kinase Inhibitor p27; Cyclin-Dependent Kinases; DNA Primers; DNA, Complementary; Enzyme Inhibitors; Female; Gene Expression; Gene Targeting; Genes, Tumor Suppressor; Heterozygote; Hyperplasia; Infertility, Female; Male; Mice; Mice, Knockout; Microtubule-Associated Proteins; Molecular Sequence Data; Phenotype; Pituitary Neoplasms; Polyenes; Retinal Dysplasia; Sirolimus; Tissue Distribution; Transforming Growth Factor alpha; Tumor Suppressor Proteins