Biomedical subjects
Publications and source records attributed to D L Myster.
Developmental regulation of the cell cycle is an important determinant of tissue size and shape. Equally important is regulated withdrawal from the cell cycle to allow cells to differentiate. Recent evidence supports a direct link between transcriptional regulation of the cell cycle machinery and cell differentiation.
During development signaling pathways coordinate cell fates and regulate the choice between cell survival or programmed cell death. The well-conserved Wingless/Wnt pathway is required for many developmental decisions in all animals. One transducer of the Wingless/Wnt signal is Armadillo/beta-catenin. Drosophila Armadillo not only transduces Wingless signal, but also acts in cell-cell adhesion via its role in the epithelial adherens junction. While many components of both the Wingless/Wnt signaling pathway and adherens junctions are known, both processes are complex, suggesting that unknown components influence signaling and junctions. We carried out a genetic modifier screen to identify some of these components by screening for mutations that can suppress the armadillo mutant phenotype. We identified 12 regions of the genome that have this property. From these regions and from additional candidate genes tested we identified four genes that suppress arm: dTCF, puckered, head involution defective (hid), and Dpresenilin. We further investigated the interaction with hid, a known regulator of programmed cell death. Our data suggest that Wg signaling modulates Hid activity and that Hid regulates programmed cell death in a dose-sensitive fashion.
The E2F family of transcription factors contributes to cell cycle control by regulating the transcription of DNA replication factors. Functional 'E2F' is a DNA-binding heterodimer composed of E2F and DP proteins. Drosophila contains two E2F genes (dE2F, dE2F2) and one DP gene (dDP). Mutation of either dE2F or dDP eliminates G(1)-S transcription of known replication factors during embryogenesis and compromises DNA replication. However, the analysis of these mutant phenotypes is complicated by the perdurance of maternally supplied gene function. To address this and to further analyze the role of E2F transcription factors in development we have phenotypically characterized mitotic clones of dDP mutant cells in the female germline. Our analysis indicates that dDP is required for several essential processes during oogenesis. In a fraction of the mutant egg chambers the germ cells execute one extra round of mitosis, suggesting that in this tissue dDP is uniquely utilized for cell cycle arrest rather than cell cycle progression. Mutation of dDP in the germline also prevents nurse cell cytoplasm transfer to the oocyte, resulting in a 'dumpless' phenotype that blocks oocyte development. This phenotype likely results from both disruption of the actin cytoskeleton and a failure of nurse cell apoptosis, each of which are required for normal cytoplasmic transfer. Lastly, we found that dDP is required for the establishment of the dorsal-ventral axis, as loss of dDP function prevents the localized expression of the EGFR ligand Gurken in the oocyte, which initiates dorsal-ventral polarity in the egg chamber. Thus we have uncovered new functions for E2F transcription factors during development, including an unexpected role in pattern formation.