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Evidence for cell-replacement repair of X-ray-induced teratogenic damage in male genital imaginal discs of Drosophila melanogaster.

Male genital imaginal discs from old (late-third-instar) larvae of Drosophila that had been X-irradiated with appropriate doses developed into severely damaged adult genitalia when implanted into old larvae, but they developed into completely normal adult genitalia when transplanted into 2-day-younger larvae. The major cause of X-ray-initiated teratogenesis in the genital disc was DNA damage because development of the genital discs of strain mei-9a with defective DNA repair was twice as sensitive as that of the wild-type strain to impairment by X-irradiation, just as larvae of this strain were twice as sensitive to killing by X-irradiation as those of the wild-type strain. Complete repair of X-ray-induced teratogenic damage in the genital discs on transplantation into young host larvae was similar in the wild-type and mei-9a strains. These results are discussed in relation to the hypothesis that repair of X-ray-induced teratogenic damage depends not on DNA repair but on replacement of damage-bearing primordial cells by healthy ones after suicidal elimination of the former.

Animals↗

Patterns of cell division in imaginal discs of Drosophila.

A transmission electron microscopic study of cell division in serially sectioned imaginal discs of early third instar fruitfly larvae revealed that mitotic cells maintain a relationship with the basal surface of the disc through thin cytoplasmic extensions abutting on vesicular material. Two patterns of cell division were discerned. In one, cell divisions were isolated and usually found near the peripodial membrane-disc epithelium junction; in the other, cell divisions were clustered. Observations on cell death and cell division in the peripodial membrane are also reported.

Animals↗

The ultrastructure of imaginal disc cells in primary cultures and during cell aggregation in continuous cell lines.

We have examined the ultrastructure of cellular vesicles in primary cultures of wing imaginal disc cells of Drosophila melanogaster. These cells maintain the apico-basal polarity characteristic of epithelial cells. The apical surfaces secrete extracellular material into the lumen of the vesicle from plasma membrane plaques at the tip of microvilli. During the course of one passage, cells from the established cell lines grow to confluence and then aggregate into discrete condensations joined by aligned bridges of cells. Cells in these aggregates are tightly packed, and there appears to be a loss of the epithelial polarity characteristic of the vesicle cells. Elongated cell extensions containing numerous microtubules are found in aggregates, and we suggest that these may be epithelial feet involved in the aggregation process. Virus particles are commonly found both within the nucleus and the cytoplasm of cells in the aggregates.

Animals↗

Compensatory eye movements during active head rotation for near targets: effects of imagination, rapid head oscillation and vergence.

Because the center of natural head rotation lies some distance behind the centers of eye rotation, the VOR has to operate with a gain substantially above 1 for there to be stable fixation of targets lying near the head. In humans, VOR gain was increased inversely proportional to fixation distance and changed with the angle of the head for very near targets. These effects were also evident when the subject imagined the target. However, this "high-gain" VOR was found to deteriorate substantially at frequencies beyond ca 2.5 Hz. In conditions without visual feedback, the VOR gain enhancement due to near fixation was disrupted by monocular viewing. When the subjects wore lenses to relax or increase accommodation, the lenses were found to have no effect on VOR gain. On the other hand, prisms of equivalent power to the lenses had a large effect whereby gain was adjusted according to the vergence state of the eyes. This suggests that VOR gain modulation is under the direct control of convergence.

Accommodation, Ocular↗

A position-specific cell surface antigen in the drosophila wing imaginal disc.

The antibody produced by the hybrid cell line DK. 1A4 recognizes an antigen present initially on all the epithelial cells of the D. melanogaster wing imaginal disc. This antigen becomes progressively restricted to cells in the dorsal region of the disc during the final larval instar. The presence of the antigen does not correlate with the specific adult structures to which the cells will eventually contribute, but rather with the position of the cells in the disc. In late discs, the line bounding the region in which the antigen persists corresponds to the boundary between the dorsal and ventral compartments are revealed by a clonal analysis of the undifferentiated disc. Together, these data suggest that the antigen's disappearance may be specific to the cells of the ventral compartment of the wing disc.

Animals↗

Interaction between dorsal and ventral cells in the imaginal disc directs wing development in Drosophila.

The adult appendages of Drosophila develop from imaginal discs. An early step in disc patterning involves the formation of developmental boundaries that subdivide the discs into compartments. Anterior and posterior compartments are established in the embryo. Later in development a new boundary originates to subdivide the wing disc into dorsal and ventral compartments, which correspond to the dorsal and ventral surfaces of the adult wing. We report here that spatially localized expression of the homeobox gene apterous (ap) specifies the identity of dorsal cells in the wing. The boundary of cell lineage restriction between dorsal and ventral compartments coincides with the limit of the domain of ap expression. Using genetic mosaics, we show that juxtaposition of dorsal and ventral cells induces formation of the wing margin. We present evidence that the dorsal-ventral boundary promotes growth and serves as a pattern-organizing center in the wing disc.

Animals↗

cAMP-dependent protein kinase and hedgehog act antagonistically in regulating decapentaplegic transcription in Drosophila imaginal discs.

Localized expression of decapentaplegic (dpp) is required for proper development of the Drosophila imaginal discs. Using genetic mosaics, we show that in the anterior compartment of appendage discs and anterior to the morphogenetic furrow in the eye disc, cells that lack cAMP-dependent protein kinase (PKA) activity ectopically express dpp. Pka- cells can influence the fate of neighboring cells to reorganize anterior patterns in appendages and trigger ectopic morphogenetic furrows in the developing retina. This organizing activity of Pka mutant cells depends on dpp activity. Our findings suggest that PKA is a component of a signaling pathway that represses dpp expression and that hh antagonizes this pathway to maintain dpp expression at the anterior-posterior compartment border and in the morphogenetic furrow.

Animals↗

A cDNA clone homologous to Drosophila F elements from an imaginal discs poly(A)+ library.

A cDNA clone (F-id1) homologous to Drosophila F elements has been isolated from a cDNA library prepared from poly(A)+ RNA derived from imaginal discs. The F-id1 insert is identical to the 3' end terminus of Fw, an element inserted at the white locus upon irradiation. The isolation of F-id1 provides the first evidence that F elements are expressed in the fruit fly life.

Animals↗

Proctolin promotes vitellogenesis onset in the imaginal molt decapitated cockroach Blaberus craniifer.

The ovarian response of the imaginal molt decapitated cockroach, Blaberus craniifer, to nanomolar quantities of synthetic proctolin was evaluated. Sites binding anti-egg proteins were detected in the basal oocyte in 67% (18 out of 27) of the treated females, indicating that vitellogenin uptake is mediated by proctolin. The injected concentration of proctolin was consistent with a physiological role. The results suggest that proctolin, a putative neurotransmitter or neuromodulator, possibly acts on a non-excitable cell, the oocyte. At this level, the precise mechanism is discussed with respect to the calcium-dependent processes involved in both the proctolin myogenic effect and vitellogenin uptake in other species of cockroach.

Animals↗

The influence of hemolymph-binding protein on juvenile hormone stability and distribution in Manduca sexta fat body and imaginal discs in vitro.

The wing discs and fat body of Manduca sexta larvae contain enzymes (i.e. carboxylesterase and epoxide hydratase) that can convert the C18 juvenile hormone (JH) to the acid, diol and acid diol. No evidence of oxidative degradation was noted. In vitro studies suggest that JH can be compartmentalized within the cells of the fat body where it is less accessible to degradative mechanisms. Experiments utilizing a hemolymph-binding protein fraction (BPF) in vitro with fat body and imaginal discs indicate that the BPF retards the uptake of JH by tissues and its subsequent degradation by tissue enzymes. BPF also appears to protect JH from degradation by enzymes released into the medium. By these mechanisms the insect can maintain elevated JH titers for relatively long periods. Binding protein may also keep JH in solution in the hemolymph allowing its rapid distribution throughout the insect. The data suggest that the binding protein plays a key role in maintaining juvenile hormone titers.

Adipose Tissue↗

Indolamines and onset of vitellogenesis in the imaginal molt-decapitated cockroach Blaberus craniifer Burm.

1. The effects of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid and N-acetyl-5-hydroxytryptamine on oocytes of Blaberus craniifer, in which vitellogenesis was prevented by imaginal molt decapitation, were investigated. 2. Sites binding anti-egg-protein antibodies were detected in the periphery of basal oocytes of treated females, with individual variability. 3. In this ovoviviparous cockroach, the onset of vitellogenesis may thus not be triggered solely by juvenile hormone, and indolamines may play a role in the uptake of haemolymphatic proteins by oocytes.

Animals↗

Expression in the central nervous system of a subset of the yema maternally acting genes during Drosophila embryogenesis. Post-embryonic expression extends to imaginal discs and spermatocytes.

The yema gene region of Drosophila melanogaster is a cluster of maternally acting genes isolated in differential screens. At least ten transcripts are encoded by the yema gene region; most of them are produced by independent transcription units (eight different transcription units). Using RNA dot-blot analysis and in situ hybridization to tissue sections, we have realized a comprehensive survey of the temporal and spatial expression of the yema transcripts. All these transcripts are maternally expressed. Five of them display a strict maternal expression. They are found exclusively in the female germ line (nurse cells and oocyte). These transcripts are still present in the embryo as maternal information. However, a subset of the yema genes also shows an embryonic and a post-embryonic expression. Interestingly, this expression is essentially restricted to the central nervous system (CNS) throughout the fly development, to the larval and pupal imaginal discs and to a subset of cells in the male gonad, the spermatocytes. Strikingly, these expression sites mainly contain proliferating and/or differentiating cells.

Animals↗

Establishment of imaginal discs and histoblast nests in Drosophila.

In Drosophila the homeotic genes of the bithorax-complex (BX-C) and Antennapedia-complex (ANT-C) specify the identity of segments. Adult segment primordia are established in the embryo as the histoblast nests of the abdomen and the imaginal discs of the head, thorax and terminalia. We have used a molecular probe for the limb primordia and in vivo culture to describe the nature of the adult primordia in mutants in which the pattern of homeotic gene expression was altered. The results suggest that the histoblast or disc 'mode' of development is initiated by the extended germ band stage through activity of the BX-C and ANT-C and is relatively inflexible thereafter [corrected].

Animals↗

A transient cell cycle shift in Drosophila imaginal disc cells precedes multipotency.

When Drosophila imaginal discs regenerate, specific groups of cells can switch disc identity so that, for example, cells determined for leg identity switch to wing. Such switches in cell determination are known as transdetermination. We have developed a system by which individual cells are marked and monitored in vivo as they transdetermine so that their proliferation, cell sizes, and differentiation are accurately traced. Here, we document that when cells transdetermine, they do not convert to a younger cell cycle. Instead, cell cycle changes precede transdetermination and are different from those observed at any time in normal development. We propose that it is not a younger but a unique cell cycle progression and a big cell size that conditions the cells for developmental plasticity.

Animals↗

Paradoxical lateralization of brain potentials during imagined foot movements.

Though each foot is controlled primarily by the contralateral hemisphere, the event-related brain potentials preceding an overt foot movement are largest over the ipsilateral side of the head. Because such "paradoxical lateralization" results from the spatial organization of the motor homunculus, it can provide a sign of motor-cortex activation. We report paradoxical lateralization in the potentials accompanying imagined foot movements, thereby demonstrating a contribution of cortical areas directly involved in movement execution.

Electroencephalography↗

Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.

BACKGROUND: The p53 transcription factor directs a transcriptional program that determines whether a cell lives or dies after DNA damage. Animal survival after extensive cellular damage often requires that lost tissue be replaced through compensatory growth or regeneration. In Drosophila, damaged imaginal disc cells can induce the proliferation of neighboring viable cells, but how this is controlled is not clear. Here we provide evidence that Drosophila p53 (dp53) has a previously unidentified role in coordinating the compensatory growth response to tissue damage. RESULTS: We find that dp53, the sole p53 ortholog in Drosophila, is required for each component of the response to cellular damage, including two separate cell-cycle arrests, changes in patterning gene expression, cell proliferation, and growth. We demonstrate that these processes are regulated by dp53 in a manner that is independent of DNA-damage sensing but that requires the initiator caspase Dronc. Our results indicate that once induced, dp53 amplifies and sustains the response through a positive feedback loop with Dronc and the apoptosis-inducing factors Hid and Reaper. CONCLUSIONS: How cell death and cell proliferation are coordinated during development and after stress is a fundamental question that is critical for an understanding of growth regulation. Our data suggest that dp53 may carry out an ancestral function that promotes animal survival through the coordination of responses leading to compensatory growth after tissue damage.

Animals↗

Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE.

This article provides information and a commentary on trials presented at the European Society of Cardiology meeting held in September 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In the CARE-HF extension study, the benefits of cardiac resynchronisation therapy (CRT) observed in the original study were maintained over an increased follow-up period. A study of oral enoximone (25-50 mg t.i.d.) in advanced heart failure (ESSENTIAL) showed limited benefit compared to placebo. The CIBIS-III study showed that heart failure therapy could be safely initiated with bisoprolol followed by the addition of enalapril. A subcutaneous ICD system (S-ICD) showed potential as an alternative to a transvenous ICD. In the ISSUE-2 study, an implantable loop recorder was used to guide therapy in patients with recurrent syncope. The selective endothelin antagonist sitaxsentan improved 6-MWT and functional class in patients with pulmonary arterial hypertension in the STRIDE-2 study. In SOFA, fish oil had no beneficial effect on the incidence of life-threatening arrhythmias in patients with an ICD. In IMAGINE, quinapril showed no benefit when administered to patients following CABG. Perindopril reduced cardiac remodelling in post-MI patients with normal LV function in PREAMI. SIRIUS-II showed encouraging results for the use of intravenous ularitide in symptomatic decompensated chronic heart failure. The ACTIVE W study of warfarin versus aspirin plus clopidogrel in atrial fibrillation has been stopped due to superiority of warfarin.

Cardiac Pacing, Artificial↗

Transdetermination in Drosophila imaginal discs: a model for understanding pluripotency and selector gene maintenance.

Drosophila imaginal disc cells have the ability to undergo transdetermination, a process whereby determined disc cells change fate to that of another disc identity. For example, leg disc cells can transdetermine to develop as wing cells. Such events can occur after mechanical disc fragmentation and subsequent regeneration. A subset of transdetermination events can be induced in situ by misexpression of the signaling gene wingless. Both fragmentation and wingless induce transdetermination by altering the expression of selector genes, which drive disc-specific developmental programs. An important future goal is to address how signaling pathways interact with chromatin structure to regulate and maintain the proper expression of selector genes.

Animals↗