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PubMed2005

Time to imagine space: a chronometric exploration of representational neglect.

When describing known places from memory, patients with left spatial neglect may mention more right- than left-sided items, thus showing representational, or imaginal, neglect. This suggests that these patients cannot either build or explore left locations in visual mental imagery. However, in place description there is no guarantee that patients are really employing visual mental imagery abilities, rather than verbal-propositional knowledge. Thus, patients providing symmetrical descriptions might be using other strategies than visual mental imagery. To address this issue, we devised a new test which strongly encourages the use of visual mental imagery. Twelve participants without brain damage and 12 right brain-damaged patients, of whom 7 had visual neglect, were invited to conjure up a visual mental image of the map of France. They subsequently had to state by pressing a left- or a right-sided key whether auditorily presented towns or regions were situated to the left or right of Paris on the imagined map. This provided measures of response time and accuracy for imagined locations. A further task, devised to assess response bias, used the words "left" or "right" as stimuli and the same keypress responses. Controls and non-neglect patients performed symmetrically. Neglect patients were slower for left than for right imagined locations. On single-case analysis, two patients with visual neglect had a greater response time asymmetry on the geographical task than predicted by the response bias task, but with symmetrical accuracy. The dissociation between response times and accuracy suggests that, in these patients, the left side of the mental map of space was not lost, but only "explored" less efficiently.

Adult↗
PubMed2006

The control of growth and differentiation of the wing imaginal disks of Manduca sexta.

During the larval feeding period, the growth of the wing imaginal disks of Lepidoptera is dependent on continuous feeding. Feeding and nutrition exert their effect via the secretion of bombyxin, the lepidopteran insulin-like hormone. When larvae stop feeding and enter the wandering stage in preparation for metamorphosis, the control of imaginal disk growth becomes feeding and nutrition-independent. Growth of the wing imaginal disks of non-feeding wandering stage Manduca sexta can be stopped by removal of the brain, indicating that a brain-derived factor is required for continued disk growth. Isolated wing disk growth in vitro requires both 20-hydroxyecdysone (20E) and either brain extract or bombyxin to achieve normal growth. In vitro, brain extracts and synthetic bombyxin have little or no effect in stimulating disk growth, but they greatly enhance the effect of 20E, indicating that 20E and bombyxin act synergistically to modulate growth of the imaginal disk. Brain extract and bombyxin induce a suite of insulin-response events in cultured wing disks, which indicate that bombyxin and 20E act through separate and synergistic pathways. The dose-response to 20E reaches a plateau at about 0.1 microg/ml. Tracheal differentiation of the wing disks can be induced to initiate in vitro by a low concentration of 20E, whereas higher concentrations of 20E only stimulate growth.

Animals↗
PubMed2001

Imagining physically impossible self-rotations: geometry is more important than gravity.

Previous studies found that it is easier for observers to spatially update displays during imagined self-rotation versus array rotation. The present study examined whether either the physics of gravity or the geometric relationship between the viewer and array guided this self-rotation advantage. Experiments 1-3 preserved a real or imagined orthogonal relationship between the viewer and the array, requiring a rotation in the observer's transverse plane. Despite imagined self-rotations that defied gravity, a viewer advantage remained. Without this orthogonal relationship (Experiment 4), the viewer advantage was lost. We suggest that efficient transformation of the egocentric reference frame relies on the representation of body-environment relations that allow rotation around the observer's principal axis. This efficiency persists across different and conflicting physical and imagined postures.

Adult↗
PubMed2002

Extracellular peptidases of imaginal discs of Drosophila melanogaster.

The imaginal discs of Drosophila melanogaster give rise to the adult epidermis during metamorphosis. During this developmental period several peptidase genes are expressed in disc cells, but there is a paucity of biochemical information regarding substrate specificity. We have used peptides and peptidyl 7-amino-4-methylcoumarin (AMC) substrates to detect several peptidases either positioned on the surface of wing discs or secreted by the imaginal cells. Using [Leu(5)]enkephalin as a substrate, a captopril sensitive dipeptidyl carboxypeptidase (angiotensin I-converting enzyme) and an amastatin-sensitive aminopeptidase were detected as prominent activities associated with intact discs. The formation of [Leu(5)]enkephalin-derived Phe was attributed to the concerted action of the D. melanogaster angiotensin I-converting enzyme (Ance) and a dipeptidase. The disc Ance also showed endopeptidic activity towards locust tachykinin-1 (LomTK-I) by cleaving the Gly-Val peptide bond, but this enzyme was not the sole endopeptidase activity associated with discs. Complete inhibition of the endopeptidic hydrolysis of the LomTK-1 by a disc homogenate required a combination of captopril and the neprilysin inhibitor, phosphoramidon, providing biochemical evidence for a neprilysin-like peptidase, in addition to Ance, in imaginal discs of D. melanogaster. Peptidyl AMC substrates for furin, prohormone convertase and tryptase provided evidence for trypsin-like serine endopeptidases in addition to the metalloendopeptidases. We conclude that imaginal discs are endowed with a variety of peptidases from different families that together are capable of hydrolyzing a broad range of peptides and proteins. Some of these peptidases might be responsible for the metabolic activation/inactivation of signaling peptides, as well as being involved in the production of dipeptides and free amino acids required for protein synthesis and osmotic balance during adult morphogenesis.

Animals↗
PubMed2000

Drosophila null slimb clones transiently deregulate Hedgehog-independent transcription of wingless in all limb discs, and induce decapentaplegic transcription linked to imaginal disc regeneration.

Drosophila Slimb (Slmb) is a F-box/WD40 protein which potentially participates in the ubiquitin proteolysis machinery. During development, Slmb is required in limb discs to repress Hedgehog (Hh) target genes, i.e. wingless (wg) and decapentaplegic (dpp), as well as the Wg signal transduction pathway. These repression functions have been proposed from studies using weak slmb alleles. Interestingly, experiments with strong slmb alleles have revealed additional mechanisms in which slmb is required, such as leg dorsal-ventral restriction. We have isolated new alleles of the slmb gene in a screen for new negative regulators of dpp: several amorphs (characterized by genetic and molecular criteria) and a cold-sensitive hypomorph. By performing somatic clone experiments with these new amorphic slmb alleles, we have determined that regulation of Dpp and Wg morphogens by Slmb could be different from what has already been published. We show here that in leg discs, lack of slmb function derepresses the transcription of wg independently of Hh signaling. We present evidence that ectopic legs resulting from slmb(-) clone induction only come from wg misexpression in the normal dpp domain, as ectopic proximo-distal axis are induced dorsally, and adult ectopic legs are often perfect with respect to antero-posterior polarity. In wing discs, transcription of wg, which is normally independent of Hh signaling, is also derepressed in the absence of slmb function. We also describe, in discs bearing amorphic slmb clones and in discs of two other slmb(-) contexts, a novel pattern of dpp expression consisting of an enlargement of the normal dpp domain. Strong evidence indicates that this dpp modification can be linked to imaginal disc regeneration following slmb(-) cell elimination. We have investigated the fate of slmb(-) clones, which disappear before adulthood, and found that two mechanisms of cell elimination can account for imaginal cell regeneration: an early apoptosis and a mechanism of sorting-out which excludes all slmb(-) clones from all imaginal discs. This result suggests that Slmb is likely to be involved, in addition to its repression role on Dpp and Wg, in some other essential cellular mechanism, as in the absence of Slmb, cell affinities are dramatically modified regardless of the deregulated morphogen and of the type of imaginal disc.

Animals↗
PubMed2003

Thinking outside the body: an advantage for spatial updating during imagined versus physical self-rotation.

Three studies examined effects of different response measures on spatial updating during self-rotation. In Experiment 1, participants located objects in an array with a pointer after physical self-rotation, imagined self-rotation, and a rotation condition in which they ignored superfluous sensorimotor signals. In line with previous research, updating performance was found to be superior in the physical self-rotation condition compared with the other 2. In Experiment 2, participants performed in identical rotation movement conditions but located objects by verbal labeling rather than pointing. Within the verbal modality, an advantage for updating during imagined self-rotation was found. In Experiment 3, participants performed physical and imagined self-rotations only and used a pointing response offset from their physical reference frames. Performance was again superior during imagined self-rotations. The results suggest that it is not language processing per se that improves updating performance but rather a general reduction of the conflict between physical and projected egocentric reference frames.

Attention↗
PubMed2002

Bombyxin is a growth factor for wing imaginal disks in Lepidoptera.

The mechanisms that control the growth rate of internal tissues during postembryonic development are poorly understood. In insects, the growth rate of imaginal disks varies with nutrition and keeps pace with variation in somatic growth. We describe here a mechanism by which the growth of wing imaginal disks is controlled. When wing imaginal disks of the butterfly Precis coenia are removed from the larva and placed in a standard nutrient-rich tissue culture medium they stop growing, suggesting that nutrients alone are not sufficient to support normal growth. Such disks can be made to grow at a normal rate by supplementing the culture medium with an optimal concentration of the steroid hormone 20-hydroxyecdysone and with hemolymph taken from growing larvae. The growth-promoting activity of the hemolymph is caused by a heat-stable factor that can be extracted from the CNS and appears to be identical to the neurohormone bombyxin, a member of the insulin family of proteins. Synthetic bombyxin stimulates growth at concentrations as low as 30 ngml, and specific antibodies to bombyxin completely remove growth-promoting activity from the hemolymph. Bombyxin evidently acts together with 20-hydroxyecdysone to stimulate cell division and growth of wing imaginal disks. It appears that the level of bombyxin in the hemolymph is modulated by the brain in response to variation in nutrition and is part of the mechanism that coordinates the growth of internal organs with overall somatic growth.

Animals↗
PubMed1998

Where the imaginal appears real: a positron emission tomography study of auditory hallucinations.

An auditory hallucination shares with imaginal hearing the property of being self-generated and with real hearing the experience of the stimulus being an external one. To investigate where in the brain an auditory event is "tagged" as originating from the external world, we used positron emission tomography to identify neural sites activated by both real hearing and hallucinations but not by imaginal hearing. Regional cerebral blood flow was measured during hearing, imagining, and hallucinating in eight healthy, highly hypnotizable male subjects prescreened for their ability to hallucinate under hypnosis (hallucinators). Control subjects were six highly hypnotizable male volunteers who lacked the ability to hallucinate under hypnosis (nonhallucinators). A region in the right anterior cingulate (Brodmann area 32) was activated in the group of hallucinators when they heard an auditory stimulus and when they hallucinated hearing it but not when they merely imagined hearing it. The same experimental conditions did not yield this activation in the group of nonhallucinators. Inappropriate activation of the right anterior cingulate may lead self-generated thoughts to be experienced as external, producing spontaneous auditory hallucinations.

Adult↗
PubMed1991

The homeotic gene Sex combs reduced of Drosophila melanogaster is differentially regulated in the embryonic and imaginal stages of development.

The Sex combs reduced (Scr) locus is unique among the genes contained within the Antennapedia complex (ANT-C) of Drosophila melanogaster in that it directs functions that are required for both cephalic and thoracic development in the embryo and the adult. Antibodies raised against protein encoded by Scr were used to follow the distribution of this gene product in embryos and imaginal discs of third instar larvae. Analysis of Scr protein accumulation in embryos hemizygous for breakpoint lesions mapping throughout the locus has allowed us to determine that sequences required for establishment of the Scr embryonic pattern are contained within a region of DNA that overlaps with the identified upstream regulatory region of the segmentation gene fushi tarazu (ftz). Gain-of-function mutations in Scr result in the presence of ectopic sex comb teeth on the first tarsal segment of mesothoracic and metathoracic legs of adult males. Heterozygous combinations of gain-of-function alleles with a wild-type Scr gene exhibit no evidence of ectopic protein localization in the second and third thoracic segments of embryos. However, mesothoracic and metathoracic leg imaginal discs can be shown to accumulate ectopically expressed Scr protein, implying a differential regulation of the Scr gene during these two periods of development. Additionally, we have found that the spatial pattern of Scr gene expression in imaginal tissues involved in the development of the adult thorax is governed in part by synapsis of homologous chromosomes in this region of the ANT-C. However, those imaginal discs that arise anteriorly to the prothorax do not appear to be sensitive to this form of gene regulation. Finally, we have demonstrated that the extent of Scr expression is influenced by mutations at the Polycomb (Pc) locus but not by mutant alleles of the zeste (z) gene. Taken together, our data suggests that Scr gene expression is differentially regulated both temporally and spatially in a manner that is sensitive to the structure of the locus.

Animals↗
PubMed1996

Identification of substrate proteins for cathepsin L that are selectively hydrolyzed during the differentiation of imaginal discs of Sarcophaga peregrina.

Previously, we showed that cathepsin L is essential for the differentiation of imaginal discs of the flesh fly [Homma, K. & Natori, S. (1994) J. Biol. Chem. 269, 15258-15264]. We have now identified imaginal disc proteins that are susceptible to digestion by cathepsin L and showed that they are selectively hydrolyzed during imaginal disc differentiation. Two of these proteins, with molecular masses of 210 and 200 kDa, were further characterized. Immunofluorescence studies suggested that they were intrinsic components of the basement membranes of various tissues. They were selectively hydrolyzed at the elongation stage of imaginal leg disc differentiation. Western blotting of embryos at various developmental stages showed that these proteins were only detected at the end of embryogenesis.

Animals↗
PubMed2003

"... As you would have them do unto you": Does imagining yourself in the other's place stimulate moral action?

Philosophers, psychologists, and religious teachers have suggested that imagining yourself in another's place will stimulate moral action. The authors tested this idea in two different situations. In Experiment 1, participants had the opportunity to assign themselves and another research participant to tasks, with one task clearly more desirable than the other. Imagining oneself in the other's place did little to increase the morality (fairness) of the decision. A different form of perspective taking, imagining the other's feelings, increased direct assignment of the other to the desirable task, apparently due to increased empathy. In Experiment 2, participants confronted a different decision: either accept an initial task assignment that would give them highly positive consequences and the other participant nothing or change the assignment so they and the other would each receive moderately positive consequences. In this situation, imagining oneself in the other's place did significantly increase moral action.

Adult↗
PubMed1983

Controlled comparison of aversive therapy and imaginal desensitization in compulsive gambling.

Twenty compulsive gamblers were randomly allocated, half to receive aversion-relief therapy and half to receive imaginal desensitization; both groups were followed-up for one year. Compared with those who received aversion-relief, gamblers who received imaginal desensitization reported a significantly greater reduction of gambling urge and behaviour; they also showed a significant reduction in trait anxiety at one year and in state anxiety at one month and one year following treatment. A high level of state anxiety at one month following treatment predicted failure to respond to treatment at one year in the subjects who received imaginal desensitization, but not in those who received aversion-relief. The relationship between reduction in anxiety and in gambling urge in response to imaginal desensitization was predicted from the theory that compulsive gambling is driven by aversive tension.

Adult↗
PubMed1991

An extensive 3' cis-regulatory region directs the imaginal disk expression of decapentaplegic, a member of the TGF-beta family in Drosophila.

The decapentaplegic (dpp) gene in Drosophila melanogaster encodes a TGF-beta-like signalling molecule that is expressed in a complex and changing pattern during development. One of dpp's contributions is to proximal-distal outgrowth of the adult appendages, structures derived from the larval imaginal disks. Appendage specific mutations of dpp fall in a 20 kb interval 3' to the known dpp transcripts. Here, we directly test the hypothesis that these mutations define an extended 3' cis-regulatory region. By analysis of germ-line transformants expressing a reporter gene, we show that sequences from this portion of the gene, termed the dppdisk region, are capable of directing expression comparable to that defined by RNA in situ hybridization. We localize two intervals of the dppdisk region that appear to account for much of the dpp spatial pattern in imaginal disks and discuss the positions of these important elements in terms of the genetics of dpp. Finally, we provide evidence to suggest that one of our constructs expresses beta-galactosidase in the early imaginal disk primordia in the embryo, at approximately the time when they are set aside from surrounding larval epidermal tissues. Thus, dpp may be involved directly in the determination of the imaginal disks.

Animals↗
PubMed1991

The relationship of decapentaplegic and engrailed expression in Drosophila imaginal disks: do these genes mark the anterior-posterior compartment boundary?

Imaginal disks, the primordia of the adult appendages in Drosophila, are divided into anterior and posterior compartments. However, the developmental role of such compartments remains unclear. The expression of decapentaplegic (dpp), a pattern formation gene required for imaginal disk development, has the intriguing property of being expressed in a line at or near the boundary between these compartments. Here, we compare the distribution of dpp-driven reporter gene expression to the pattern of expression of the engrailed (en) gene, known to be required for the maintenance of the compartment boundary. Using confocal microscopy to obtain single cell resolution, we have determined that the majority of the en+ imaginal disk cells expressing the dpp-driven reporter genes about those cells expressing en, while a small percentage of dpp reporter gene expressing cells also express en. In posterior regions of en mutant disks, where compartmentalization is abnormal, we observe ectopic expression of the dpp-driven reporter genes. We conclude that the pattern of dpp expression in imaginal disks is delimited in part through the direct or indirect repression by engrailed. Our results lead us to question the widely held assumption that the anterior edge of en expression demarcates the A/P compartment boundary.

Animals↗
PubMed1993

Gene expression during imaginal disc regeneration detected using enhancer-sensitive P-elements.

When imaginal disc fragments from Drosophila are cultured in adult female hosts, they either duplicate the part of the pattern specified by the fate map, or regenerate to replace the missing part. The new tissue is added by proliferation of a small number of cells from the cut edge, brought together when the wound heals to form a regeneration blastema. Specification of the new pattern has been explained by assuming interactions among cells of different positional value in the regeneration blastema. In order to identify genes which might mediate these events, we screened over eight hundred independently isolated autosomal insertions of an enhancer-sensitive P-element, for altered lac-z expression in regenerating discs following cell death induced by a temperature-sensitive cell-lethal mutation. Two further screens divided the positive lines into four groups based on appropriate timing of the lac-z response in the cell-lethal mutant background and the expected response to an alternate source of cell death. Expression in wing disc fragments cultured in vivo was most frequent in the target class defined by the screens. In this direct test, lac-z expression was found in 23 lines and in most cases was spatially and temporally correlated with the formation of the regeneration blastema. Our results suggest a very substantial transcriptional response during the early stages of imaginal disc regeneration. lac-z expression in control imaginal discs, embryos and adult ovaries of the positive lines was also assayed. The selected insertions included: a small class expressed only in discs undergoing regeneration and apparently not at any other stage, possibly representing genes active exclusively in regeneration; a larger class expressed in the embryo or during oogenesis, but not normally in imaginal discs, as expected for functions recruited from earlier stages of the developmental program; and finally a class with spatially patterned expression in normal discs. This class included several insertions with expression associated with compartment boundaries, including one at the decapentaplegic (dpp), and one at the crumbs (crb) locus, a growth factor homologue, and an EGF-repeat gene respectively. Some of the expression patterns observed in cultured disc fragments provide evidence for cell communication in the regeneration blastema.

Animals↗
PubMed1993

Control of imaginal cell development by the escargot gene of Drosophila.

Mutations in the escargot (esg) locus, which codes for a zinc-finger-containing protein with similarity to the product of the snail gene, cause a variety of defects in adult structures such as loss of abdominal cuticle and malformation of the wings and legs. esg RNA is expressed in wing, haltere, leg and genital imaginal discs and in abdominal histoblast nests in the embryo. Expression in imaginal tissues is also found in third instar larvae. In esg mutant larvae, normally diploid abdominal histoblasts replicate their DNA without cell division and become similar in appearance to the polytene larval epidermal cells. A similar phenotype was also found in imaginal discs of larvae mutant for both esg and the Drosophila raf gene. These results suggest that one of the normal functions of esg may be the maintenance of diploidy in imaginal cells.

Abdomen↗
PubMed2004

Dynamics of decapentaplegic expression during regeneration of the Drosophila melanogaster wing imaginal disc.

Regeneration of an imaginal disc involves highly ordered proliferation and pattern regulation of the newly formed tissue. Although the general principles of imaginal disc regeneration have been extensively studied, knowledge of the underlying molecular mechanisms is far from complete. Results from other model organisms suggest that regeneration is the result of local recapitulation of the normal patterning genes. To analyze the dynamics of one major Drosophila patterning gene, decapentaplegic (dpp), in wing imaginal disc regeneration, a vital GFP reporter together with iontophoretic cell labeling were used. Our observations reveal that the restoration of compartment-border-specific dpp expression is a common event in imaginal disc regeneration. However, we did not find evidence of an upregulation of dpp expression during the regeneration process.

Animals↗
PubMed2005

Role of Jun N-terminal Kinase (JNK) signaling in the wound healing and regeneration of a Drosophila melanogaster wing imaginal disc.

When a fragment of a Drosophila imaginal disc is cultured in growth permissive conditions, it either regenerates the missing structures or duplicates the pattern present in the fragment. This kind of pattern regulation is known to be epimorphic, i.e. the new pattern is generated by proliferation in a specialized tissue called the blastema. Pattern regulation is accompanied by the healing of the cut surfaces restoring the continuous epithelia. Wound healing has been considered to be the inductive signal to commence regenerative cell divisions. Although the general outlines of the proliferation dynamics in a regenerating imaginal disc blastema have been well studied, little is known about the mechanisms driving cells into the regenerative cell cycles. In this study, we have investigated the role of Jun N-terminal Kinase (JNK) signaling in the wound healing and regeneration of a Drosophila wing imaginal disc. By utilizing in vivo and in vitro culturing of incised and fragmented discs, we have been able to visualize the dynamics in cellular architecture and gene expression involved in the healing and regeneration process. Our results directly show that homotypic wound healing is not a prerequisite for regenerative cell divisions. We also show that JNK signaling participates in imaginal disc wound healing and is regulated by the physical dynamics of the process, as well as in recruiting cells into the regenerative cell cycles. A model describing the determination of blastema size is discussed.

Animals↗