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1.
Pavlik LL Bezgina EN Dzeban DA Moshkov DA 《Neuroscience and behavioral physiology》2005,35(5):453-456
The pyroantimonate method was used to study the distribution of calcium ions in the mixed synapses of Mauthner neurons after exposure to substances altering the electrotonic conductivity of these synapses mediated by gap junctions (GJ). Ecdysone, an agent which increases GJ conductivity, produced precipitates of calcium pyroantimonate coating the whole postsynaptic surface of the GJ area, making them strongly asymmetrical. Precipitate granules were also seen to appear in the clefts of desmosome-like contacts (DLC). Chlorpromazine, which decreases GJ conductivity, produced precipitates in GJ clefts and on the pre- and postsynaptic membranes. No precipitate formed in DLC clefts. These results demonstrate that ecdysone acts as an agent selectively increasing GJ conductivity without affecting DLC function. Chlorpromazine had a double action, blocking conduction through both GJ and DLC. Thus, studies of agents altering GJ permeability require consideration of the possibility that they may interact with actin-containing structures also involved in the transport of the electrotonic signal.Translated from Morfologiya, Vol. 125, No. 3, pp. 32–35, May–June, 2004. 相似文献
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Background
Dilp8-mediated inhibition of ecdysone synthesis and pupation in holometabolous insects maintains developmental homeostasis through stringent control of timing and strength of molting signals. We examined reasons for normal pupation but early pupal death observed in certain cases.Results
Overexpression of activated Ras in developing eye/wing discs inhibited Ptth expression in brain via upregulated JNK signaling mediated Dilp8 secretion from imaginal discs, which inhibited ecdysone synthesis in prothoracic gland after pupariation, leading to death of ~25- to 30-hour-old pupae. Inhibition of elevated Ras signaling completely rescued early pupal death while post-pupation administration of ecdysone to organisms with elevated Ras signaling in eye discs partially rescued their early pupal death. Unlike the earlier known Dilp8 action in delaying pupation, hyperactivated Ras mediated elevation of pJNK signaling in imaginal discs caused Dilp8 secretion after pupariation. Ectopic expression of certain other transgene causing pupal lethality similarly enhanced pJNK and early pupal Dilp8 levels. Suboptimal ecdysone levels after 8 hours of pupation prevented the early pupal metamorphic changes and caused organismal death.Conclusions
Our results reveal early pupal stage as a novel Dilp8 mediated post-pupariation checkpoint and provide further evidence for interorgan signaling during development, wherein a peripheral tissue influences the CNS driven endocrine function.5.
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Xueping Hu Xiaojuan Ma Jialin Cui Haishan Liu Bin Zhu Jin Xie Pei Liang Li Zhang 《Chemical biology & drug design》2021,97(1):184-195
Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three‐step virtual screening procedure uses a three‐dimensional pharmacophore model, docking and Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) rescoring routine. A novel hit ( VS14 ) with good binding activity against Plutella xylostella EcR was identified from a library of over 200,000 chemicals. Subsequently, the 1‐phenyl‐4‐cyano‐5‐aminopyrazole scaffold and twelve EcR ligands were synthesized. Their IC50 values against Plutella xylostella EcR ranged from 0.64 to 23.21 μm . Furthermore, a preliminary analysis of the structure–activity relationship for novel scaffolds provided a basis for designing new ligands with improved activity. 相似文献
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Brandon Mark Liliana Bustos-Gonzlez Guadalupe Cascallares Felipe Conejera John Ewer 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(27)
The daily rhythm of adult emergence of holometabolous insects is one of the first circadian rhythms to be studied. In these insects, the circadian clock imposes a daily pattern of emergence by allowing or stimulating eclosion during certain windows of time and inhibiting emergence during others, a process that has been described as “gating.” Although the circadian rhythm of insect emergence provided many of the key concepts of chronobiology, little progress has been made in understanding the bases of the gating process itself, although the term “gating” suggests that it is separate from the developmental process of metamorphosis. Here, we follow the progression through the final stages of Drosophila adult development with single-animal resolution and show that the circadian clock imposes a daily rhythmicity to the pattern of emergence by controlling when the insect initiates the final steps of metamorphosis itself. Circadian rhythmicity of emergence depends on the coupling between the central clock located in the brain and a peripheral clock located in the prothoracic gland (PG), an endocrine gland whose only known function is the production of the molting hormone, ecdysone. Here, we show that the clock exerts its action by regulating not the levels of ecdysone but that of its actions mediated by the ecdysone receptor. Our findings may also provide insights for understanding the mechanisms by which the daily rhythms of glucocorticoids are produced in mammals, which result from the coupling between the central clock in the suprachiasmatic nucleus and a peripheral clock located in the suprarenal gland.Circadian clocks impose a daily rhythmicity to the behavior and physiology of most multicellular organisms, in which they are believed to provide a mechanism for synchronizing the behavior and physiology of individuals to the daily planetary changes in light and temperature (1). One of the first circadian rhythms to be studied is the rhythm of adult emergence of holometabolous insects (eclosion) (2–4). Eclosion occurs at the end of metamorphosis and is typically restricted to dawn or dusk, depending on the species. Population eclosion profiles show a daily rhythmicity that persists under conditions of constant darkness and temperature and is temperature-compensated, thereby showing the hallmarks of a circadian rhythm (e.g., refs. 4 to 6).In holometabolous insect species in which this rhythm has been studied, the circadian clock controls the timing of adult emergence by exerting its influence at the very end of adult development. For example, Pittendrigh and Skopik (6) demonstrated in Drosophila victoria that overt developmental markers for the progression through metamorphosis, such as the time of eye or bristle pigmentation, occur at times that only depend on the number of hours since the start of metamorphosis and are not affected by changes in the light:dark (LD) cycle. By contrast, eclosion (the final step of metamorphosis) is the only event whose timing is sensitive to the LD regime, with flies always emerging during the morning. Similarly, in Drosophila melanogaster, Qiu and Hardin (7) followed the timing of wing pigmentation to show that animals that pigment their wings during the day will primarily emerge during the following day, whereas those that do so at night are delayed an extra ca. 12 h and wait until the light period 2 d later, indicating that the clock exerts its control after the wings have pigmented, during the final day of metamorphosis. Thus, in order to eclose, the insect must have completed metamorphosis and also be within the appropriate time window.Because the clock intervenes at the end of adult development, the process through which it controls the time of emergence has been described as “gating,” in which emergence is inhibited during certain windows of time and stimulated and/or allowed during others. Although the circadian rhythm of eclosion was one of the first to be studied starting almost 100 y ago (2–4), there is still no clear mechanistic understanding of how this gating process occurs. Nevertheless, so far it has been viewed as a process that is independent of any developmental process. In this scenario, animals that completed metamorphosis prematurely would be prevented from eclosing until the appropriate eclosion gate were opened by the circadian clock (5, 6, 8). However, another possibility is that the clock sets the time of emergence by controlling the timecourse of completion of metamorphosis. Although both scenarios would produce a gated eclosion, they differ mechanistically in fundamental ways. In particular, the first “permissive” gating mechanism predicts that animals could complete metamorphosis at different times prior to emergence and that the clock would then only open or close the window leading to eclosion, depending on the time of the day. By contrast, a “developmental” gating mechanism predicts that animals emerging within a specific gate would speed up or slow down their molt in order to complete metamorphosis in time to emerge during the appropriate gate. In this scenario, gating would be a consequence of the synchronization of metamorphosis. Since in at least some insect species, the titers of the molting hormone, ecdysone (E), express a circadian rhythm (9, 10), a clock control of metamorphosis is a plausible scenario.Here, we analyzed the timecourse of the final stages of Drosophila metamorphosis with single-animal resolution and show that the clock gates eclosion by regulating, primarily, the moment when the final steps of metamorphosis are initiated. We also show that the clock exerts its action by regulating not the levels of the molting hormone itself but that of its actions mediated by the E receptor. Our findings may also provide insights for understanding the mechanisms by which the daily rhythms of glucocorticoid (GC) are produced in mammal, which also depend on the coupling between a central clock, located in the suprachiasmatic nucleus (SCN), and a peripheral clock, located in the suprarenal endocrine gland (11). 相似文献
8.
M F Meister J L Dimarcq C Kappler C Hetru M Lagueux R Lanot B Luu J A Hoffmann 《Molecular and cellular endocrinology》1985,41(1):27-44
A high specific activity tritiated ecdysone precursor, 2,22,25-trideoxyecdysone, was used to probe the capacity of various embryonic and larval tissues to perform the last 3 hydroxylation steps in ecdysone biosynthesis. Embryos at early stages of development, prior to the differentiation of their endocrine glands and embryonic heads, thoraces and abdomens of later stages, were found to have the capacity to hydroxylate the precursor to ecdysone. Larval epidermis and fat body are also able to transform 2,22,25-trideoxyecdysone into ecdysone; Malpighian tubules and midgut hydroxylate the precursor at C-2 but are apparently unable to hydroxylate both at C-22 and C-25. Larval prothoracic glands convert the precursor to ecdysone at a very efficient rate, which is 1-2 magnitudes higher than that of the other tissues investigated; several data argue for the existence of a privileged sequence of hydroxylations, C-25, C-22, C-2, in the larval prothoracic glands. 相似文献
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Ras signaling modulates activity of the ecdysone receptor EcR during cell migration in the Drosophila ovary. 总被引：1，自引：0，他引：1
Jennifer F Hackney Christina Pucci Erin Naes Leonard Dobens 《Developmental dynamics》2007,236(5):1213-1226
Ecdysone Receptor (EcR) mediates effects of the hormone ecdysone during larval molts, pupal metamorphosis, and adult female oogenesis. In the ovary, egg chamber formation requires interactions between the somatic follicle cell (FC) epithelium and the germ line nurse cell/oocyte cyst. Previous work has shown EcR is required in the germ line for egg chamber maturation, and here we examine EcR requirements in the FC at late stages of oogenesis. EcR protein is ubiquitous in the FC but its activity is restricted, visualized by activity of the "ligand sensor" hs-GAL4-EcR ligand binding domain fusion and EcRE-lacZ reporter gene expression. GAL4-EcR is activated in the FC by an ecdysone agonist and repressed by tissue-specific Ras GTPase signals. To determine the significance of restricted sites of EcR activity in the FC, we used targeted misexpression of the dominant negative EcR (EcR-DN) molecules EcR(F645A) and EcR(W650A). EcR-DN expression at stage 10 reduced EcRE-lacZ expression in the nurse cell FC and resulted in abnormal FC migrations, including aberrant centripetal migration and dorsal appendage tube formation, leading to the formation of cup-shaped eggs with shortened, branched dorsal appendages at stage 14. Clones of FC expressing EcR-DN displayed cell-autonomous increases in DE-cadherin expression and abnormal epithelial junction formation. EcR-DN expression caused thin eggshell phenotypes that correlated with both reduced levels of chorion gene expression and reduction in chorion gene amplification. Our results indicate that tissue-specific modulation of EcR activity by the Ras signaling pathway refines temporal ecdysone signals that regulate FC differentiation and cadherin-mediated epithelial cell shape changes. 相似文献
