Biomedical subjects

T Volk

Publications and source records attributed to T Volk.

At least 37 records · Page 2Linked to original sources

PubMed2000

Ferritin oxidation in vitro: implication of iron release and degradation by the 20S proteasome.

Ferritin, the major iron storage protein in mammalian cells, was treated with various concentrations of different oxidants: xanthine/xanthine oxidase, Sin-1 (3-morpholinosydnonimine, purchased from Alexis, Grunberg, Germany), DEA-NO (Diethylamine NONOate, purchased from Calblochem-Novabiochem, Schwalbach, Germany), and hydrogen peroxide. The proteolytic susceptibility towards the isolated 20S proteasome of untreated ferritin and oxidized ferritin was measured in parallel with the iron liberated by these oxidants. With increasing hydrogen peroxide, Sin-1, and xanthine oxidase concentrations, the measured proteasomal degradation of ferritin also increased. At higher oxidant concentrations, however, the proteolytic susceptibility began to decrease. The oxidation of ferritin by DEA-NO was accompanied by a lesser increase of proteolytic susceptibility in comparison with the effects of the other oxidants. Addition of DEA-NO to Sin-1 suppressed the increase in proteolytic susceptibility of ferritin, whereas adding xanthine/xanthine oxidase had no additional effect. Iron was liberated readily from ferritin as a result of the oxidation process, although the increase in proteolytic susceptibility was not always correlated to the iron release. In fact, the degradation of oxidatively damaged ferritin was not accompanied by a further increase of free iron. Therefore, we conclude that the proteasome is a secondary antioxidative defense system that degrades only nonfunctional ferritin.

Cysteine Endopeptidases↗

PubMed2000

Influence of heparin and hirudin on endothelial binding of antithrombin in experimental thrombinemia.

OBJECTIVE: During the last decade, experimental and clinical evidence has accumulated that antithrombin (AT) exerts anti-inflammatory effects when given in high doses. Meanwhile, AT substitution has been shown to significantly increase prostacyclin release. However, the link between endothelial AT binding and anti-inflammatory AT effects remains to be established in vivo, although heparin has been shown to counteract anti-inflammatory AT effects. We hypothesized that the administration of heparin in endotoxin-challenged rats would decrease endothelial AT binding and systemic prostacyclin concentrations. DESIGN: Prospective, randomized, controlled experimental in vivo study. SETTING: Research laboratory of a university hospital. ANIMALS: Fifty-six Wistar rats. INTERVENTIONS: Baseline values of coagulation variables were measured in six animals. Forty of 50 Wistar rats in the study groups were given endotoxin (50 mg x kg(-1) iv) and were treated with saline (group LPS), AT (15 units x kg(-1) x hr(-1)) (LPS+AT), AT and heparin (80 IU x kg(-1) x hr(-1)), or AT and hirudin (0.12 mg x kg(-1) x hr(-1)); the other 10 received saline instead of endotoxin and were treated with AT alone. Before endotoxin application, a tracheostomy was performed, and venous and arterial catheters were inserted for blood sampling and infusion. MEASUREMENTS: Intravital endothelial AT binding was studied by using fluorescence isothiocyanate-marked antibodies during intravital microscopy of intestinal submucosal venules. Systemic prostacyclin, thrombin-AT complex, and fibrinogen concentrations were measured after 4 hrs. Intergroup differences were tested by Kruskal-Wallis analysis of variance on ranks. MAIN RESULTS: AT and AT + heparin were equally effective in inhibiting systemic procoagulant turnover as reflected by fibrinogen concentrations. Only the administration of AT + hirudin significantly prevented fibrinogen consumption (p < .05). In contrast with all other treatments, the administration of heparin significantly reduced intravital endothelial AT binding (p < .05). However, prostacyclin concentrations were similarly increased in all endotoxin-challenged study groups irrespective of the anticoagulatory treatment. CONCLUSIONS: There is evidence that heparin in contrast with hirudin prevents AT from being bound to the endothelial cell surface in this experimental model. Under low-dose AT substitution, systemic prostacyclin concentrations do not depend on whether heparin or hirudin is used for thrombin inhibition. These results support the view that heparin may counteract anti-inflammatory AT effects by keeping AT away from its endothelial binding sites; however, the results question the view that decreased endothelial prostacyclin release is solely responsible.

Animals↗

PubMed1999

Relationship between transient outward K+ current and Ca2+ influx in rat cardiac myocytes of endo- and epicardial origin.

1. The transient outward K+ current (Ito) is a major repolarizing ionic current in ventricular myocytes of several mammals. Recently it has been found that its magnitude depends on the origin of the myocyte and is regulated by a number of physiological and pathophysiological signals. 2. The relationship between the magnitude of Ito, action potential duration (APD) and Ca2+ influx (QCa) was studied in rat left ventricular myocytes of endo- and epicardial origin using whole-cell recordings and the action potential voltage-clamp method. 3. Under control conditions, in response to a depolarizing voltage step to +40 mV, Ito averaged 12.1 +/- 2.6 pA pF-1 in endocardial (n = 11) and 24.0 +/- 2.6 pA pF-1 in epicardial myocytes (n = 12; P < 0.01). APD90 (90 % repolarization) was twice as long in endocardial myocytes, whereas QCa inversely depended on the magnitude of Ito. L-type Ca2+ current density was similar in myocytes from both regions. 4. To determine the effects of controlled reductions of Ito on QCa, recordings were repeated in the presence of increasing concentrations of the Ito inhibitor 4-aminopyridine. 5. Inhibition of Ito by as little as 20 % more than doubled QCa in epicardial myocytes, whereas it had only a minor effect on QCa in myocytes of endocardial origin. Further inhibition of Ito led to a progressive increase in QCa in epicardial myocytes; at 90 % inhibition of Ito, QCa was four times larger than the control value. 6. We conclude that moderate changes in the magnitude of Ito strongly affect QCa primarily in epicardial regions. An alteration of Ito might therefore allow for a regional regulation of contractility during physiological and pathophysiological adaptations.

Action Potentials↗

PubMed1999

Vein expression is induced by the EGF receptor pathway to provide a positive feedback loop in patterning the Drosophila embryonic ventral ectoderm.

The presence of a single EGF receptor in Drosophila is contrasted by multiple ligands activating it. This work explores the role of two ligands, Spitz and Vein, in the embryonic ventral ectoderm. Spitz is a potent ligand, whereas Vein is an intrinsically weak activating ligand. We show that secreted Spitz emanating from the midline, triggers expression of vein in the ventral-most cell rows, by inducing expression of the ETS domain transcription factor Pointed P1. In the absence of Vein, lateral cell fates are not induced when Spitz levels are compromised. The positive feedback loop of Vein generates a robust mechanism for patterning the ventral ectoderm.

Animals↗

PubMed1999

Monocyte stimulation by reactive oxygen species: role of superoxide and intracellular Ca2+.

OBJECTIVE: Production of reactive oxygen species has generally been linked to inflammatory processes. Whether the presence of superoxide and hydrogen peroxide affects mononuclear cell function was investigated with an in vitro model using isolated human mononuclear cells. MATERIALS AND METHODS: Human mononuclear cells were isolated from buffy coat. Toxicity was measured with Trypan blue exclusion, secreted TNF-alpha was measured with an ELISA, reactive oxygen species within mononuclear cells were quantified with dichlorodihydrofluorescein diacetate fluorescence, intracellular TNF-alpha was measured with flow cytometry and fluorescence microscopy. RESULTS: The enzymatic production of superoxide caused a dose-dependent increase in TNF-alpha synthesis, whereas hydrogen peroxide was ineffective. Flow cytometric measurements and immunofluorescence microscopy demonstrated that monocytes were the main TNF-alpha producing population. This proinflammatory reaction was further characterized by pharmacologically investigating Ca2+ signalling pathways. Superoxide stimulated TNF-alpha secretion was inhibited by intracellular Ca2+-buffers (MAPT-AM and BAPT-AM) or VOC operating antagonists (diltiazem and verapamil) and only to a small extent by pharmacological inhibitors of ligand-gated pathways (TMB-8 and SKF 96368). CONCLUSION: We propose that superoxide activates human mononuclear cells in a Ca2+-dependent manner.

Calcium↗

PubMed1999

Influence of different gases and intraperitoneal instillation of antiadherent or cytotoxic agents on peritoneal tumor cell growth and implantation with laparoscopic surgery in a rat model.

BACKGROUND: A generally accepted approach to prevent tumor implantation with laparoscopic surgery does not exist. Alternative gases in combination with intraperitoneal instillation of different antiadherent or cytotoxic agents have not been evaluated. METHODS: The effect of taurolidine, heparin, and povidone-iodine on the growth of colon adenocarcinoma DHD/K12/TRb was measured in rats undergoing laparoscopy with carbon dioxide (n = 40), helium (n = 40), or xenon (n = 40). In the procedure, 10(4) tumor cells were administered intraperitoneally, and pneumoperitoneum was established over 30 min at 8 mmHg with the different gases. The rats additionally received intraperitoneal instillation with one of the following: 1 ml of Ringer's solution, 1 ml of 0.5% taurolidine, 1 ml 0.5% taurolidine with heparin (10 U/ml), or 1 ml 0.25% of povidone-iodine. Tumor growth was measured after 4 weeks. RESULTS: Median intraperitoneal tumor weight was lower in rats receiving taurolidine (CO(2): 10 mg; helium: 50 mg; xenon: 39.5 mg) or taurolidine with heparin (CO(2): 4 mg; helium: 4.5 mg; xenon: 46.5 mg) in all gas groups than in the control groups (CO(2): 427 mg; helium: 268 mg; xenon: 345 mg) (p < 0.001). Whereas povidone-iodine caused significantly lower tumor growth in the CO(2) group (56.5 mg) (p < 0.01), the combination of helium (145 mg) and xenon (457 mg) with povidone-iodine produced no reduction of tumor growth as compared with the control groups (helium: 268 mg; xenon: 345 mg). CONCLUSIONS: Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum. Only povidone-iodine caused significant decrease of tumor growth in combination with CO(2). The combination of xenon and povidone-iodine should not be used in patients with cancer because of increased tumor growth.

Adenocarcinoma↗

PubMed1999

Singling out Drosophila tendon cells: a dialogue between two distinct cell types.

The precise match between somatic muscles and their epidermal attachment cells is achieved through a continuous dialogue between these two cell types. Whereas tendon cells direct myotube migration and final patterning, the muscles are essential for the maintenance of the fate of tendon cells. The Drosophila neuregulin-like ligand, Vein, and its receptor, the epidermal growth factor receptor (Egfr), are critical components in the inductive signaling process that takes place between muscles and tendon cells. Additional gene products that relay the Vein-Egfr effect in Drosophila are conserved in the vertebrate neuregulin-mediated cascade. This review describes genetic and molecular aspects of the muscle-tendon inductive processes in Drosophila, and compares them with the relevant mechanisms in the vertebrate embryo.

Animals↗

PubMed1999

Oxidized proteins as a marker of oxidative stress during coronary heart surgery.

The measurement of the degree of oxidative stress in patients often causes problems because of the lack of useful parameters. Therefore, we used an ELISA technique to evaluate serum protein carbonyls as a parameter of oxidative stress in patients during coronary heart surgery. Protein carbonyls were detected in serum samples of 14 patients undergoing coronary surgery and cardiopulmonary artery bypass grafting. A clear 2- to 3-fold increase in protein carbonyls in serum samples taken from human venous coronary sinus could be detected in the reperfusion period of the heart. We compared these data with markers of oxidative stress previously used, such as the glutathione status and the lipid peroxidation product malondialdehyde (MDA). Strong correlations of the protein carbonyl formation with MDA (r2 = 0.86) and oxidized glutathione (r2 = 0.81) were found in the early reperfusion stage. Increased levels of oxidized glutathione and MDA were detected only in the early reperfusion period. In contrast, the serum protein carbonyl content remained elevated for several hours, indicating a considerably slower serum clearance of oxidized proteins compared with that of lipid peroxidation products and the normalization of the glutathione status. We therefore concluded that the measurement of serum carbonyls by this ELISA technique is suitable to detect oxidative stress in serum samples of patients. The relative stability of the parameter makes the protein carbonyl detection even more valuable for clinical purposes.

Aged↗

PubMed1999

Growing wheat in Biosphere 2 under elevated CO2: observations and modeling.

Spring wheat (Triticum aestivum L., cv. Yecora Rojo) was grown in the intensive agricultural biome (IAB) of Biosphere 2 during the l995-l996 winter/spring season. Environmental conditions were characterized by a day/night temperature regime of 27/17 degrees C, relative humidity (RH) levels around 45%, mean atmospheric CO2 concentration of 450 ppmv, and natural light conditions with mean intensities about half of outside levels. Weekly samples of above-ground plant matter were collected throughout the growing season and phenological events recorded. A computer model, CERES-Wheat, previously tested under both field and controlled conditions, was used to simulate the observed crop growth and to help in data analysis. We found that CERES-Wheat simulated the data collected at Biosphere 2 to within 10% of observed, thus suggesting that wheat growth inside the IAB was comparable to that documented in other environments. The model predicts phenological stages and final dry matter (DM) production within l0% of the observed data. Measured DM production rates, normalized for light absorbed by the crop. suggested photosynthetic efficiencies intermediate between those observed under optimal field conditions and those recorded in NASA-Controlled Ecological Life-Support Systems (CELSS). We suggest that such a difference can be explained primarily in terms of low light levels inside the IAB, with additional effects due to elevated CO2 concentrations and diffuse light fractions.

Agriculture↗

PubMed1999

The balance between two isoforms of the Drosophila RNA-binding protein how controls tendon cell differentiation.

In Drosophila, a tendon cell is selected from a group of equipotent precursors following its interaction with a muscle cell. This interaction results in elevated levels of the transcription factor Stripe in the future tendon cells. Here we show that the balance between two distinct forms of the RNA-binding protein How maintains low levels of Stripe at the precursor stage and high levels in the mature tendon. The long, nuclear-specific protein How(L) downregulates Stripe protein levels at the precursor stage by binding stripe mRNA and inhibiting its nuclear export. This inhibition is likely to be counteracted by the short How(S) protein, present in both nucleus and cytoplasm, which is upregulated in the muscle-bound tendon cell following EGF receptor activation.

Alternative Splicing↗

PubMed1999

[Forced opioid detoxification under general anesthesia--a new challenge for anesthetists and intensive care physicians].

Treatment of opioid addicts by means of competitive opioid receptor antagonists was developed at the University of Vienna in 1987 by Loimer and co-workers. They compared two withdrawal regimens: The short Opiate withdrawal using a staggered naloxone regimen and the rapid opiate detoxification during general anesthesia by means of high doses of naloxone. Based on the latter concept, various modifications have been developed world-wide using either naloxone or as an alternative, naltrexone, an antagonist available for oral administration only. However, there are considerable objections to opioid detoxification during general anasthesia. The main criticism is based an the supposedly unacceptable high risk:benefit-ratio, the higher costs, the lack of psycho-social support, and the lack of prospective studies. However, first results suggest that rapid detoxification procedures are more successful in decreasing relapse than methods which are based on psychiatric treatment alone. As sympathetic hyperfunction is common in rapid detoxification procedures using high doses of opioid receptor antagonists, it is essential to avoid severe autonomic imbalance with possible subsequent impairment of organ functions. To prevent those disturbances, general anesthesia plays an important role. So far, there is almost no information about such methods in the anesthesiological literature. In this article the clinical relevance of such methods is discussed summarizing both the available literature and our own experience and we conclude that rapid opioid detoxification under general anesthesia is a safe and efficient method to suppress withdrawal symptoms. This treatment may be of benefit in patients who particularly suffer from severe withdrawal symptoms and who have failed repeatedly to complete conventional withdrawal.

Anesthesia, General↗

PubMed1999

Phasic temperature and photoperiod control for soybean using a modified CROPGRO model.

A modified CROPGRO model is applied to phasic temperature and photoperiod control in order to optimize soybean production for NASA's program in Advanced Life Support. Baseline model simulations were established using data from soybean temperature experiments conducted at elevated CO2 levels (1100 micromol mol-1) at Utah State University (USU). The model simulations show little advantage in using phasic temperature control alone to increase average seed yield rate over the USU experimental values. However, simulations that combine phasic control of temperature (two phases) and photoperiod (two phases) do indicate the potential to improve seed yield (in g m-2 day-1) by approximately 15% over those currently obtained experimentally at USU for soybean cultivar Hoyt. This temperature and photoperiod phasing is experimentally practical. The simulations suggest extending photoperiods over those typically used experimentally during later phases of the crop life cycle, which would lengthen grain fill duration and thereby increase mass per seed. The model simulations indicate that the timing, and duration of extended photoperiods would be very important due to possible reductions in seed number m-2. Besides affecting seed yield directly, the model simulations suggest that such reductions may also cause feedback inhibition of photosynthesis due to low seed sink strength at elevated CO2 levels.

Biomass↗

PubMed1998

Kakapo, a novel cytoskeletal-associated protein is essential for the restricted localization of the neuregulin-like factor, vein, at the muscle-tendon junction site.

In the Drosophila embryo, the correct association of muscles with their specific tendon cells is achieved through reciprocal interactions between these two distinct cell types. Tendon cell differentiation is initiated by activation of the EGF-receptor signaling pathway within these cells by Vein, a neuregulin-like factor secreted by the approaching myotube. Here, we describe the cloning and the molecular and genetic analyses of kakapo, a Drosophila gene, expressed in the tendons, that is essential for muscle-dependent tendon cell differentiation. Kakapo is a large intracellular protein and contains structural domains also found in cytoskeletal-related vertebrate proteins (including plakin, dystrophin, and Gas2 family members). kakapo mutant embryos exhibit abnormal muscle-dependent tendon cell differentiation. A major defect in the kakapo mutant tendon cells is the failure of Vein to be localized at the muscle-tendon junctional site; instead, Vein is dispersed and its levels are reduced. This may lead to aberrant differentiation of tendon cells and consequently to the kakapo mutant deranged somatic muscle phenotype.

Animals↗

PubMed1998

Stimulation of monocytes and platelets by short-chain phosphatidylcholines with and without terminal carboxyl group.

Oxidation of unsaturated phosphatidylcholine (PC) produces fragmented phospholipids which have similar bioactivities as the platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-PC). Since a large number of molecular species are produced upon PC oxidation, the active ingredients have not been identified. We synthesized several short-chain PCs which are known to be characteristic PC oxidation products to test their PAF-like activity. The synthetic PCs contained palmitoyl or hexadecyl residues (both C16) in sn-1 position, and propionyl (C3), valeroyl (C5), succinyl (C4 with omega-carboxyl), glutaroyl (C5 with omega-carboxyl), or suberoyl (C8 with omega-carboxyl) residues in sn-2 position. Biological activity was measured by: (1) increase of intracellular calcium in human monocytes; (2) [3H]serotonin release from rabbit platelets; and (3) aggregation of human platelets. Specificity of the cellular response was tested by inhibition with the PAF-receptor antagonists BN 52021 and WEB 2086. Synthetic PC oxidation products activated both monocytes and platelets in a PAF-specific manner. The effective concentration varied with respect to assay system and chemical structure. In general, 1-hexadecyl-PCs were more effective than 1-palmitoyl-PCs, while increasing chain length in sn-2 position lowered biological activity. However, several 1-palmitoyl-PCs activated monocytes in concentrations between 10-8 and 10-6 M. In contrast, platelets were less susceptible to 1-palmitoyl-PCs. No significant difference was found between 2-valeroyl-PC (C5 with omega-methyl) and 2-glutaroyl-PC (C5 with omega-carboxyl). The data suggest that typical products of PC oxidation, containing propionyl, succinyl, or glutaroyl residues in sn-2 position, display PAF-like activity at micromolar concentrations.

Animals↗

PubMed1998

An interplay between two EGF-receptor ligands, Vein and Spitz, is required for the formation of a subset of muscle precursors in Drosophila.

Activation of the Drosophila EGF-receptor (DER) is spatially and temporally controlled by the release of its various ligands. DER and its ligand Spitz mediate the formation of specific somatic muscle precursors. We show that a second DER ligand, Vein, complements the activity of Spitz in the development of various somatic muscle precursors. In vn mutant embryos, the DER-dependent muscle precursors do not form in some of the segments. This phenotype is significantly enhanced in embryos carrying only one copy of wild type spitz. Our analysis suggests that Vein activation of DER differs qualitatively from that of Spitz in that it does not lead to the expression of the inhibitory protein Argos, possibly leading to a continuous activation of the DER signaling pathway.

Animals↗

PubMed1998

Hyperprocalcitonemia in patients with noninfectious SIRS and pulmonary dysfunction associated with cardiopulmonary bypass.

BACKGROUND: The incidence of noninfectious systemic inflammatory response syndrome (SIRS) associated with coronary artery bypass surgery and the potential role of several inflammatory parameters as early markers of pulmonary dysfunction induced by cardiopulmonary bypass (CPB) were investigated. METHODS: Forty patients undergoing elective coronary artery bypass surgery were studied prospectively. Perioperative lung function was monitored using the lung injury score introduced by Murray and colleagues, by measuring venous admixture (Qs/Qt), and, in some cases, by measuring extravascular lung water. Serum concentrations of the inflammatory parameters (procalcitonin, interleukin-6, sL-selectin, leukocyte elastase, neopterin, leukocyte counts, and C-reactive protein) were determined sequentially. The American College of Chest Physicians-Society of Critical Care Medicine classification system was used to diagnose SIRS. RESULTS: According to the entry criteria, SIRS developed in 17 (42%) patients after operation. Nine patients of this group showed signs of acute pulmonary impairment, whereas patients without SIRS had no lung injury. In all patients with acute lung injury, distinct increases in procalcitonin concentrations ranging from 5.1 to 14.3 ng/ml were measured. In patients with SIRS but without acute lung injury and in patients without SIRS, none or only negligible increases in serum concentrations of procalcitonin were seen. Compared with procalcitonin, other inflammatory parameters investigated were less sensitive and less specific to indicate pulmonary dysfunction secondary to CPB. CONCLUSIONS: Procalcitonin seems to be an appropriate parameter indicating the early development of severe noninfectious SIRS and for predicting pulmonary dysfunction secondary to CPB.

Aged↗

PubMed1998

The impact of laparoscopy with carbon dioxide versus helium on immunologic function and tumor growth in a rat model.

BACKGROUND: The pathogenesis of port site recurrences after laparoscopic surgery for malignant disease is still unknown. Whether different gases used to establish pneumoperitoneum have an influence on immunologic function and therefore on promotion of tumor growth has not yet been investigated. METHODS: Tumor growth of colon adenocarcinoma DHD/K12/TRb was evaluated in a rat model after insufflation either with CO2 (n = 25) or helium (n = 25) and in a control group (n = 25). Tumor growth was measured subcutaneously and intraperitoneally 5 weeks after insufflation. Beside tumor growth, immunologic changes (peripheral leukocyte subpopulations, plasma levels of TNFalpha and IL-10) were evaluated during the perioperative course in all animals. RESULTS: Subcutaneous tumor growth was promoted by the CO2 (99 +/- 55 mg; p < 0.01) compared to the helium (40 +/- 41 mg) and control groups (36 +/- 33 mg). Total intraperitoneal tumor weight was 718 +/- 690 mg in the CO2 group compared to the helium (549 +/- 233 mg) and control groups (521 +/- 221 mg). While peripheral leukocyte subpopulations only differed between the laparoscopic groups and the control group during the perioperative course, TNFalpha plasma levels were significantly decreased and IL-10 plasma levels significantly increased in the CO2 group compared to the helium and control groups in the postoperative course. CONCLUSION: The insufflation of CO2 promotes tumor growth compared to the helium and control groups in a rat model. In addition, increased tumor growth was associated with a significant increase in IL-10 and a decrease in TNFalpha plasma levels.

Adenocarcinoma↗

PubMed1997

The Drosophila neuregulin homolog Vein mediates inductive interactions between myotubes and their epidermal attachment cells.

Inductive interactions between cells of distinct fates underlie the basis for morphogenesis and organogenesis across species. In the Drosophila embryo, somatic myotubes form specific interactions with their epidermal muscle attachment (EMA) cells. The establishment of these interactions is a first step toward further differentiation of the EMA cells into elongated tendon cells containing an organized array of microtubules and microfilaments. Here we show that the molecular signal for terminal differentiation of tendon cells is the secreted Drosophila neuregulin-like growth factor Vein produced by the myotubes. Although vein mRNA is produced by all of the myotubes, Vein protein is secreted and accumulates specifically at the muscle-tendon cell junctional site. In loss-of-function vein mutant embryos, muscle-dependent differentiation of tendon cells, measured by the level of expression of specific markers (Delilah and beta1 tubulin) is blocked. When Vein is expressed in ectopic ectodermal cells, it induces the ectopic expression of these genes. Our results favor the possibility that the Drosophila EGF receptor DER/Egfr expressed by the EMA cells functions as a receptor for Vein. We show that Vein/Egfr binding activates the Ras pathway in the EMA cells leading to the transcription of the tendon-specific genes, stripe, delilah, and beta1 tubulin. In Egfr1F26 mutant embryos that lack functional Egfr expression, the levels of Delilah and beta1 tubulin are very low. In addition, the ability of ectopic Vein to induce the expression of Delilah and beta1 tubulin depends on the presence of functional Egfrs. Finally, activation of the Egfr signaling pathway by either ectopically secreted Spitz, or activated Ras, leads to the ectopic expression of Delilah. These results suggest that inductive interactions between myotubes and their epidermal muscle attachment cells are initiated by the binding of Vein, to the Egfr on the surface of EMA cells.

Animals↗