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Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. During the progression of AD, massive neuronal degeneration occurs in the late stage of the disease; however, the molecular mechanisms responsible for this neuronal loss remain unknown. AβpE3-42 (an N-terminal-truncated amyloid-β peptide that begins with pyroglutamate at the third position) is produced during late-stage AD. It also aggregates more rapidly in vitro and exhibits greater toxicity in neurons than full-length Aβ1-42. In the present study, we established a Drosophila melanogaster model that expresses Aβ3-42E3Q, which effectively produces AβpE3-42, and investigated the function of AβpE3-42 using the photoreceptor neurons of Drosophila. AβpE3-42 induced caspase-dependent apoptosis and caused progressive degeneration in photoreceptor neurons. Mutations in ER stress response genes or the administration of an inhibitor of the ER stress response markedly suppressed the degeneration phenotype, suggesting that the ER stress response plays an important role in neurodegeneration caused by AβpE3-42. We also confirmed that human Tau-dependent apoptotic induction was strongly enhanced by AβpE3-42. Thus, AβpE3-42 expression system in the fly may be a promising new tool for studying late-onset neurodegeneration in AD.

DOI： 10.1093/hmg/ddx346

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The "moth-eye" structure, which is observed on the surface of corneal lens in several insects, supports anti-reflective and self-cleaning functions due to nanoscale protrusions known as corneal nipples. Although the morphology and function of the "moth-eye" structure, are relatively well studied, the mechanism of protrusion formation from cell-secreted substances is unknown. In Drosophila melanogaster, a compound eye consists of approximately 800 facets, the surface of which is formed by the corneal lens with nanoscale protrusions. In the present study, we sought to identify genes involved in "moth-eye" structure, formation in order to elucidate the developmental mechanism of the protrusions in Drosophila. We re-examined the aberrant patterns in classical glossy-eye mutants by scanning electron microscope and classified the aberrant patterns into groups. Next, we screened genes encoding putative structural cuticular proteins and genes involved in cuticular formation using eye specific RNAi silencing methods combined with the Gal4/UAS expression system. We identified 12 of 100 candidate genes, such as cuticular proteins family genes (Cuticular protein 23B and Cuticular protein 49Ah), cuticle secretion-related genes (Syntaxin 1A and Sec61 ββ subunit), ecdysone signaling and biosynthesis-related genes (Ecdysone receptor, Blimp-1, and shroud), and genes involved in cell polarity/cell architecture (Actin 5C, shotgun, armadillo, discs large1, and coracle). Although some of the genes we identified may affect corneal protrusion formation indirectly through general patterning defects in eye formation, these initial findings have encouraged us to more systematically explore the precise mechanisms underlying the formation of nanoscale protrusions in Drosophila.

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BACKGROUND: In standard cell division, the cells undergo karyokinesis and then cytokinesis. Some cells, however, such as cardiomyocytes and hepatocytes, can produce binucleate cells by going through mitosis without cytokinesis. This cytokinesis skipping is thought to be due to the inhibition of cytokinesis machinery such as the central spindle or the contractile ring, but the mechanisms regulating it are unclear. We investigated them by characterizing the binucleation event during development of the Drosophila male accessory gland, in which all cells are binucleate. RESULTS: The accessory gland cells arrested the cell cycle at 50 hours after puparium formation (APF) and in the middle of the pupal stage stopped proliferating for 5 hours. They then restarted the cell cycle and at 55 hours APF entered the M-phase synchronously. At this stage, accessory gland cells binucleated by mitosis without cytokinesis. Binucleating cells displayed the standard karyokinesis progression but also showed unusual features such as a non-round shape, spindle orientation along the apico-basal axis, and poor assembly of the central spindle. Mud, a Drosophila homolog of NuMA, regulated the processes responsible for these three features, the classical isoform Mud(PBD) and the two newly characterized isoforms Mud(L) and Mud(S) regulated them differently: Mud(L) repressed cell rounding, Mud(PBD) and Mud(S) oriented the spindle along the apico-basal axis, and Mud(S) and Mud(L) repressed central spindle assembly. Importantly, overexpression of Mud(S) induced binucleation even in standard proliferating cells such as those in imaginal discs. CONCLUSIONS: We characterized the binucleation in the Drosophila male accessory gland and examined mechanisms that regulated unusual morphologies of binucleating cells. We demonstrated that Mud, a microtubule binding protein regulating spindle orientation, was involved in this binucleation. We suggest that atypical functions exerted by three structurally different isoforms of Mud regulate cell rounding, spindle orientation and central spindle assembly in binucleation. We also propose that Mud(S) is a key regulator triggering cytokinesis skipping in binucleation processes.

DOI： 10.1186/s12861-014-0046-5

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The Drosophila male accessory gland has functions similar to those of the mammalian prostate gland and the seminal vesicle, and secretes accessory gland proteins into the seminal fluid. Each of the two lobes of the accessory gland is composed of two types of binucleate cell: about 1,000 main cells and 40 secondary cells. A well-known accessory gland protein, sex peptide, is secreted from the main cells and induces female postmating response to increase progeny production, whereas little is known about physiological significance of the secondary cells. The homeodomain transcriptional repressor Defective proventriculus (Dve) is strongly expressed in adult secondary cells, and its mutation resulted in loss of secondary cells, mononucleation of main cells, and reduced size of the accessory gland. dve mutant males had low fecundity despite the presence of sex peptide, and failed to induce the female postmating responses of increased egg laying and reduced sexual receptivity. RNAi-mediated dve knockdown males also had low fecundity with normally binucleate main cells. We provide the first evidence that secondary cells are crucial for male fecundity, and also that Dve activity is required for survival of the secondary cells. These findings provide new insights into a mechanism of fertility/fecundity.

DOI： 10.1371/journal.pone.0032302

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Language：English   Publishing type：Research paper (scientific journal)  

The Drosophila middle midgut cells derived from the endoderm develop into four distinct types of cell. Of these cells, copper cells have invaginated microvillar membranes on their apical surface, and they are involved in two distinct functions, i.e., copper absorption and acid secretion. The homeobox gene defective proventriculus (dve) is expressed in the midgut, and two transcripts, type A (~4.9. kb) and type B (~3.5. kb), have been identified. We isolated the deletion allele dveE181 that completely removes the first exon for type-A (dve-A) transcript. Dve expression pattern in dve-A mutant background indicates that isoform switching is dynamically regulated in a cell-type specific manner. Using RNAi for dve-A, we examined spatial and temporal requirement of the Dve-A activity. Early Dve-A activity is required to repress isoform switching in copper cells, and for establishment of two gut functions. Late Dve-A activity in copper cells, but not in adjacent interstitial cells, is required for acid secretion, while the activity is redundantly required in both cells for the copper absorptive function. Furthermore, ectopic type-B expression in larval copper cells specifically impaired the copper absorptive function. These results provide insight into molecular mechanisms to establish functional specificity. © 2011 Elsevier Ireland Ltd.

DOI： 10.1016/j.mod.2011.02.003

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