Btk29A-mediated tyrosine phosphorylation of armadillo/β-catenin promotes ring canal growth in Drosophila oogenesis.

Drosophila Btk29A is the ortholog of mammalian Btk, a Tec family nonreceptor tyrosine kinase whose deficit causes X-linked agammaglobulinemia in humans. The Btk29AficP mutation induces multiple abnormalities in oogenesis, including the growth arrest of ring canals, large intercellular bridges that allow the flow of cytoplasm carrying maternal products essential for embryonic development from the nurse cells to the oocyte during oogenesis. In this study, inactivation of Parcas, a negative regulator of Btk29A, was found to promote Btk29A accumulation on ring canals with a concomitant increase in the ring canal diameter, counteracting the Btk29AficP mutation.

fat facets induces polyubiquitination of Imd and inhibits the innate immune response in Drosophila.

The IMD pathway is one of the major regulators of the innate immune response in Drosophila. Although extensive analysis of the IMD pathway has been carried out, precise mechanisms for how each target gene of the pathway is down-regulated remain to be clarified. Here, we carried out genetic screening and found that fat facets (faf), which encodes a deubiquitinating enzyme, inhibited the expression of the target genes of the IMD pathway.

Negative modulation of bone morphogenetic protein signaling by Dullard during wing vein formation in Drosophila.

Studies in Xenopus have shown that the C-terminal domain phosphatase-like domain (CPD) phosphatase Dullard is essential for proper neural development via inhibition of bone morphogenetic protein (BMP) signaling receptors. In contrast, the orthologous budding yeast Nem1 and human Dullard have been shown to dephosphorylate the phosphatidate phosphatases yeast Smp2/Pah1 and human Lipin, and the relationship between phospholipid metabolism and BMP signaling remain unsolved. Here we report evidence that the Dullard-Lipin phosphatase cascade in Drosophila can regulate BMP signaling, most likely by affecting the function of the nuclear envelope.

Functional analysis of Toll-related genes in Drosophila.

The Drosophila genome encodes a total of nine Toll and related proteins. The immune and developmental functions of Toll and 18Wheeler (18W) have been analyzed extensively, while the in vivo functions of the other Toll-related proteins require further investigation. We performed transgenic experiments and found that overexpression of Toll-related genes caused different extents of lethality and developmental defects.

A fat body-derived IGF-like peptide regulates postfeeding growth in Drosophila.

Members of the insulin family of peptides have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. Here we show that Drosophila insulin-like peptide 6 (DILP6), which is structurally similar to vertebrate insulin-like growth factor (IGF), is predominantly expressed in the fat body, a functional equivalent of the vertebrate liver and adipocytes. This expression occurs during the postfeeding stage under the direct regulation of ecdysteroid.

Essential roles of myosin phosphatase in the maintenance of epithelial cell integrity of Drosophila imaginal disc cells.

Reorganization of the actin cytoskeleton and contraction of actomyosin play pivotal roles in controlling cell shape changes and motility in epithelial morphogenesis. Dephosphorylation of the myosin regulatory light chain (MRLC) by myosin phosphatase is one of the key events involved. Allelic combinations producing intermediate strength mutants of the Drosophila myosin-binding subunit (DMBS) of myosin phosphatase showed imaginal discs with multilayered disrupted morphologies, and extremely mislocated cells, suggesting that DMBS is required to maintain proper epithelial organization.

Involvement of the mitochondrial protein translocator component tim50 in growth, cell proliferation and the modulation of respiration in Drosophila.

Allelic mutants exhibiting growth defects in Drosophila were isolated. Molecular cloning identified the responsible gene as a budding yeast Tim50 ortholog, and thus it was named tiny tim 50 (ttm50). The weak allele (ttm50(Gp99)) produced small flies due to reduced cell size and number, and growth terminated at the larval stage in the strong alleles (ttm50(IE1) and ttm50(IE2)).

Mi-2 chromatin remodeling factor functions in sensory organ development through proneural gene repression in Drosophila.

Mi-2, the central component of the nucleosome remodeling and histone deacetylation (NuRD) complex, is known as an SNF2-type ATP-dependent nucleosome remodeling factor. No morphological mutant phenotype of Drosophila Mi-2 (dMi-2) had been reported previously; however, we found that rare escapers develop into adult flies showing an extra bristle phenotype. The dMi-2 enhanced the phenotype of ac(Hw49c), which is a dominant gain-of-function allele of achaete (ac) and produces extra bristles.

Armadillo/Pangolin regulates PCNA and DREF promoter activities.

Here we show that Armadillo and Pangolin (dTCF), downstream effectors of the Wingless (Wg) signal transduction pathway, activate transcription of the important DNA replication-related genes encoding Drosophila proliferating cell nuclear antigen (PCNA) and DNA replication-related element-binding factor (DREF). By transient luciferase expression assays and band mobility shift assays, we demonstrated the PCNA gene to be a direct target gene for the Armadillo/Pangolin complex. Using a GAL4-UAS system, stimulation of the PCNA gene by Armadillo/Pangolin was confirmed in adult females.

Barrier-to-autointegration factor plays crucial roles in cell cycle progression and nuclear organization in Drosophila.

Barrier-to-autointegration factor (BAF) is potentially a DNA-bridging protein, which directly associates with inner nuclear membrane proteins carrying LEM domains. These features point to a key role in regulation of nuclear function and organization, dependent on interactions between the nuclear envelope and chromatin. To understand the functions of BAF in vivo, Drosophila baf null mutants generated by P-element-mediated imprecise excision were analyzed.

Transcription control of a gene for Drosophila transcription factor, DREF by DRE and cis-elements conserved between Drosophila melanogaster and virilis.

A DNA replication-related element (DRE)-binding factor (DREF) has been revealed to be an important transcription factor for activating promoters of cell proliferation and differentiation related genes. The amino acid sequences of DREF are conserved in evolutionary separate Drosophila species, Drosophila melanogaster (Dm) and Drosophila virilis (Dv) in three regions. In the present study, evidence was obtained that there are several highly conserved regions in the 5' flanking region between the DmDREF and DvDREF genes.

Characterization of the dCaMKII-GAL4 driver line whose expression is controlled by the Drosophila Ca2+/calmodulin-dependent protein kinase II promoter.

Transgenic flies that can drive GAL4 expression under the control of the 7 kb 5'-region of the Drosophila Ca(2+)/calmodulin-dependent protein kinase II (dCaMKII) gene (dCaMKII-GAL4) were established. Characteristic features of this dCaMKII-GAL4 driven reporter expression were compatible with the endogenous dCaMKII expression pattern: The dCaMKII-GAL4 driven reporter gene was expressed preferentially in the central nervous system of the embryo and larvae. Reporter expression was also observed in the brain, thoracic ganglion, and gut of the adult.

Drosophila myosin phosphatase and its role in dorsal closure.

Myosin phosphatase negatively regulates nonmuscle myosin II through dephosphorylation of the myosin regulatory light chain (MRLC). Its regulatory myosin-binding subunit, MBS, is responsible for regulating the catalytic subunit in response to upstream signals and for determining the substrate specificity. DMBS, the Drosophila homolog of MBS, was identified to study the roles of myosin phosphatase in morphogenesis.