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[Inhalation induction].

OBJECTIVES: To clarify how pharmacokinetics explains the speed and quality of mask induction with sevoflurane alone or associated with adjuvants. To describe the various techniques to obtain adequate anaesthesia for laryngeal mask or tracheal tube insertion. To give the indications, contra-indications and complications of this technique. DATA SOURCES: Data were obtained from Medline and authors clinical experience. DATA SYNTHESIS: Inhalation induction in adults affords rapid loss of consciousness similar to the intravenous route if high concentrations of sevoflurane are delivered to the patient. Time of laryngeal mask or tracheal tube insertion is longer but may be reduced by adding N(2)O and/or a low opioid dose. The interest of benzodiazepine as premedication is not established but is highly probable when considering its potentiating effect on halogenated agents. Without any adjuvant, inhalation induction maintains spontaneous ventilation better than propofol. This justifies favouring this technique when difficult intubation is anticipated. This technique is associated to less or similar cardiovascular effects than intravenous propofol. However, some patients exhibit dramatic tachycardia and arterial pressure increase that should lead to caution in cardiovascular disabled patients. This sympathetic hyperactivity occurs with epileptiform EEG activity that was never associated with postanaesthesia mental dysfunction. In aged or cardiac patients, by reducing sevoflurane concentrations from 8% to 2% (or by 2% decreasing steps), the cardiovascular effect of this inhalation induction is better than propofol. This technique is contra-indicated in HMS susceptible patients and those suffering from a myopathy, or patients with intracranial hypertension, a full stomach or active gastro-oesophageal reflux. CONCLUSION: Inhalation induction in adults remains little used in common clinical practice. Technical improvement by adding opioids and education of anesthetists should increase the diffusion of this alternative method to intravenous induction of anaesthesia.

Anesthesia, Inhalation↗

Stat1-independent induction of SOCS-3 by interferon-gamma is mediated by sustained activation of Stat3 in mouse embryonic fibroblasts.

Using microarray technology, we previously demonstrated that IFN-gamma induces suppressor of cytokine signaling-3 (SOCS-3) in Stat1-/- mouse embryonic fibroblasts and bone marrow-derived macrophages. In this study, we have investigated the mechanism by which SOCS-3 is induced by Stat1-independent signal transduction pathway. Tyrosine kinases Jak1 and Jak2 are required for SOCS-3 induction by IFN-gamma in mouse embryonic fibroblasts. IFN-gamma stimulated strong and sustained activation of Stat1 whereas Stat3 activation was weak and transient in wild-type fibroblasts. In contrast, Stat3 is activated strongly and in a sustained manner in Stat1-/- fibroblasts. The Src kinase inhibitor SU6656 suppressed IFN-gamma activation of Stat3 in both wild-type and Stat1-/- fibroblasts. However, SU6656 inhibited IFN-gamma induction of SOCS-3 completely in Stat1-/- but not in wild-type fibroblasts. Knock down of Stat3 by short interfering RNA abrogated Stat3 activation and SOCS-3 induction by IFN-gamma in Stat1-/- fibroblasts. In human fibrosarcoma cell line 2fTGH, IFN-gamma activated Stat1 but not Stat3. SOCS-3 induction by IFN-gamma is strictly Stat1-dependent. The Stat1 docking site is required for SOCS-3 induction by IFN-gamma in human lung adenocarcinoma cells. We propose a model in which sustained activation of Stat1 or Stat3 mediates SOCS-3 induction by IFN-gamma in wild-type and Stat1-/- mouse embryonic fibroblasts, respectively.

Adenocarcinoma↗

Investigating the procedural variables that determine whether rats will display negative anticipatory contrast or positive induction.

Previous studies have demonstrated that consumption of a low-valued food substance may decrease if access to a high-valued substance will soon be available (negative anticipatory contrast). Research has also demonstrated that responding for a low-valued reinforcer may increase if responding for a high-valued reinforcer will soon be possible (positive induction). The present experiment employed rats to respond in a procedure similar to that typically used to produce negative anticipatory contrast. The goal was to determine what factors contribute to when a contrast or an induction effect will occur. Based on previous research, the influence of auditory cues, temporal delays, food deprivation, and location of substance delivery were investigated. Auditory cues and temporal delays did little to influence whether subjects increased or decreased their consumption of 1% sucrose when access to 32% sucrose was upcoming. The appearance of contrast or induction was related to level of deprivation, with deprivation promoting induction. Which effect occurred also depended on whether subjects consumed the two substances from one spout in one location (induction) or from two different spouts in two different locations (contrast). The present results help identify the procedural link(s) between these two effects. They also provide insight to why positive induction may occur (i.e., higher-order place conditioning).

Acoustic Stimulation↗

Mechanisms of mindfulness: emotion regulation following a focused breathing induction.

The current study investigated whether a 15 min recorded focused breathing induction in a normal, primarily undergraduate population would decrease the intensity and negativity of emotional responses to affectively valenced picture slides and increase willingness to remain in contact with aversive picture slides. The effects of the focused breathing induction were compared with the effects of 15 min recorded inductions of unfocused attention and worrying. The focused breathing group maintained consistent, moderately positive responses to the neutral slides before and after the induction, whereas the unfocused attention and worry groups responded significantly more negatively to the neutral slides after the induction than before it. The focusing breathing group also reported lower negative affect and overall emotional volatility in response to the post-induction slides than the worry group, and greater willingness to view highly negative slides than the unfocused attention group. The lower-reported negative and overall affect in response to the final slide blocks, and greater willingness to view optional negative slides by the focused breathing group may be viewed as more adaptive responding to negative stimuli. The results are discussed as being consistent with emotional regulatory properties of mindfulness.

Adaptation, Psychological↗

2-Methoxyestradiol and paclitaxel have similar effects on the cell cycle and induction of apoptosis in prostate cancer cells.

2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with promise for cancer chemotherapy, including advanced prostate cancer. We have focused on events related to cell cycle arrest (G1 and G2/M) and induction of apoptosis in human prostate cancer cells. Treatment with 2-ME increased cyclin B1 protein and its associated kinase activity followed by later inhibition of cyclin A-dependent kinase activity and induction of apoptosis. Similar results were obtained with paclitaxel (taxol), a clinically relevant agent used to treat advanced prostate cancer. Cyclin-dependent kinase inhibitors prevented 2-ME and paclitaxel-mediated increase in cyclin B1-dependent kinase activity and blocked induction of apoptosis. Reduction of X-linked inhibitor of apoptosis (XIAP) protein by 2-ME and paclitaxel correlated with increased apoptosis. Lower doses of 2-ME and paclitaxel resulted in G1 (but not G2/M) cell cycle arrest in the p53 wild type LNCaP cell line, but with minimal induction of apoptosis. We suggest that 2-ME and paclitaxel-mediated induction of apoptosis in prostate cancer cells requires activation of cyclin B1-dependent kinase that arrests cells in G2/M and subsequently leads to the induction of apoptotic cell death.

2-Methoxyestradiol↗

New insights into the mechanism of imposex induction in the dogwhelk Nucella lapillus.

In an attempt to clarify the mechanism(s) of tributyltin-mediated imposex induction in females of the neogastropod Nucella lapillus, dogwhelks collected in an almost imposex free population were exposed to several treatments for a 3 month-period, and the effects on imposex induction and testosterone/estradiol levels were evaluated. As a positive control, tributyltin (50 ng TBT Sn/L) clearly induced imposex and led to a significant increase in the severity of the phenomenon. In contrast, although a selective P450 aromatase inhibitor (formestane at 0.3 mg/L) was capable of imposex induction, it failed to increase its severity. A vertebrate androgen receptor (AR) antagonist (cyproterone acetate at 1.25 mg/L) in combination with TBT completely blocked the imposex induction capacity of TBT. On the other hand, an estrogen receptor antagonist (tamoxifen at 0.3 mg/L) rendered no effect. The determination of steroid levels in female specimens revealed that TBT induces an elevation of free testosterone (but not the total amount, free+esterified), while the co-administration of the anti-androgen and TBT was able to rescue the increase of free testosterone levels. Despite a minor decrease in the amount of testosterone-fatty acid esters in the TBT group, significant differences in esterified testosterone were not found among treatments. On the contrary, free estradiol levels were elevated in the TBT, anti-androgens and TBT plus anti-androgens groups. These results indicate that free estradiol biosynthesis in TBT-exposed females does not seem to be affected. Overall, our results demonstrate that a selective aromatase inhibitor can induce imposex in N. lapillus but not to a similar extent of TBT, which may suggest the involvement of other mechanism in imposex induction, besides aromatase inhibition. Additionally, the study points to the involvement of AR receptors in imposex induction.

Animals↗

Differential involvement of left prefrontal cortex in inductive and deductive reasoning.

While inductive and deductive reasoning are considered distinct logical and psychological processes, little is known about their respective neural basis. To address this issue we scanned 16 subjects with fMRI, using an event-related design, while they engaged in inductive and deductive reasoning tasks. Both types of reasoning were characterized by activation of left lateral prefrontal and bilateral dorsal frontal, parietal, and occipital cortices. Neural responses unique to each type of reasoning determined from the Reasoning Type (deduction and induction) by Task (reasoning and baseline) interaction indicated greater involvement of left inferior frontal gyrus (BA 44) in deduction than induction, while left dorsolateral (BA 8/9) prefrontal gyrus showed greater activity during induction than deduction. This pattern suggests a dissociation within prefrontal cortex for deductive and inductive reasoning.

Adult↗

Labor induction abortion utilizing trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor.

Labor induction abortion in the second trimester is a difficult problem in developing countries because antiprogestins are either not available or unaffordable. When prostaglandins are used alone for labor induction abortion without antiprogestin pretreatment, the induction to delivery interval and the treatment failure rate increase. Trilostane, an inhibitor of 3beta-hydroxysteroid dehydrogenase enzyme system, was given to 93 women between 13 and 19 weeks gestation. The trilostane dosage used was 120 mg twice daily for the first 24 h, and then 240 mg twice daily for the next 24 h. The women returned after 48 h for hospital admission. The women were randomized to three different misoprostol regimens: low-dose vaginal group (200 microg every 4 h), high-dose vaginal group (initial dose of 400 microg followed by 200 microg every 4 h) and vaginal-oral group (400 microg vaginally followed by 200 microg orally every 4 h). The median induction to abortion times were 17, 8.3 and 9.4 h, respectively. The latter two groups had significantly shorter induction to delivery times (p<.05). The most common side effects were a burning feeling in the face (47.7%) and nausea (13.3%). Overall, trilostane side effects were mild and self-limiting and did not interfere with therapy. In conclusion, trilostane can be given as out-patient therapy prior to admission for prostaglandin administration in labor induction abortion.

3-Hydroxysteroid Dehydrogenases↗

Active induction management of labor for diabetic pregnancies at term; mode of delivery and fetal outcome--a single center experience.

OBJECTIVES: To evaluate the mode of delivery in diabetic pregnancies at term following induction of labor with vaginal application of prostaglandin E2 (PGE2), and to identify possible predictors of successful vaginal delivery. PATIENTS AND METHODS: The study group consisted of 105 women with diabetic pregnancies at term admitted for induction of labor; 84 (80%) had gestational diabetes (GDM) and 21 (20%) type 1 diabetes. Findings were compared with women who underwent elective induction of labor (n=115), and women with normal spontaneous onset of labor (n=510). Women with previous cesarean section (CS) were excluded from both study and control groups. RESULTS: Maternal age and gravidity were significantly higher in the study group than the control groups (age: 31.4+/-5, 28+/-5.0 and 28.1+/-4.8 years, respectively; gravidity: 3.0+/-1.9, 2.5+/-1.6, and 2.1+/-1.4, respectively; P<0.001 for both) and gestational age and nulliparity rate were significantly lower (gestational age: 38.6+/-1.1, 40.2+/-1.3 and 39.3+/-2.7 weeks, respectively; nulliparity: 34.6, 45.2, 51.6%, respectively; P<0.002 for both). There were no between-group differences in the incidence of oligohydramnios, number of PGE2 applications used, birth weight, rate of non-reassuring fetal heart rate pattern leading to CS, and rate of low 5 min Apgar score (<7). The rate of CS in the study group (18.2%) was significantly higher than in the spontaneous labor group (9%) but similar to the elective induction group (14.8%). On stepwise analysis, only nulliparity (OR 4.56, 95% CI 1.11-18.67, P=0.035) was independently and significantly associated with increased risk of CS. Within the study group (R2=0.257, P=0.002), type 1 diabetes (OR 2.4, 95% CI 1.04-5.51) was independently and significantly associated with increased risk of CS. CONCLUSION: In diabetic pregnancies, induction of labor at term with vaginal PGE2 is successful in approximately 82% of patients, but yields a significantly higher CS rate compared to uncomplicated pregnancies. Nulliparity and diagnosis of type 1 diabetes are independently and significantly associated with increased risk of CS. CONDENSATION: In diabetic pregnancies, induction of labor at term is successful in 82% of patients, but yields higher CS rates compared to uncomplicated pregnancies.

Adult↗

Induction of labor with misoprostol in pregnancies with advanced maternal age.

OBJECTIVE: The objective was to compare the efficacy and complications of intravaginal misoprostol application with oxytocin infusion for induction of labor in advanced aged pregnancies with a Bishop score of < 6. STUDY DESIGN: A hundred advanced aged (> or = 35 years) pregnant patients with a Bishop score of < 6 were randomized into two groups. The first group (50 patients) received 50 microg intravaginal misoprostol four times with 4 h intervals and the second group received oxytocin infusion for induction of labor starting from 2 mIU/min and was increased every 30 min with 2 mIU/min increments up to a maximum of 40 mIU/min. The time from induction to delivery, the route of delivery, fetal outcome, and maternal complications were recorded. Statistical analyses were performed using the Mann-Whitney U, Chi-squared and t tests to determine differences between the two groups. A p value < or = 0.05 was considered significant. RESULTS: Misoprostol was superior for induction of labor in advanced aged pregnancies with Bishop score of < 6, as the mean time from induction to delivery was 9.61 +/- 4.12 h and 11.46 +/- 4.86 h in the misoprostol and oxytocin groups respectively, with a significant difference between the groups (p = 0.04). The rate of vaginal delivery was higher in the misoprostol group (84.0%) than in the oxytocin group (80.0%), but the difference did not reach significance (p = 0.60). The rates of placental abruption and postpartum hemorrhage were similar in both groups and no cases of uterine rupture occurred. The 1- and 5-min mean Apgar scores were 6.98 +/- 1.17 to 9.08 +/- 0.99 and 6.88 +/- 1.81 to 9.00 +/- 1.35 in the misoprostol and oxytocin groups respectively, with no significant differences between the groups (p = 0.74, p = 0.83). No cases of asphyxia were present. The rate of admission to the neonatal intensive care unit was similar in both groups. CONCLUSION: Intravaginal misoprostol seems to be an alternative method to oxytocin in the induction of labor in advanced aged pregnant women with low Bishop scores, as it is efficacious, cheap, and easy to use. But large studies are necessary to clarify safety with regard to the rare complications such as uterine rupture.

Administration, Intravaginal↗

Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin (Sangstat).

BACKGROUND: Cytolytic induction therapy with anti-thymocyte globulin (ATG) should induce effective immunosuppression, with a low rate of rejection in the initial phase after heart transplantation. Induction therapy with ATG allows post-operative renal recovery without the negative effects of highly nephrotoxic cyclosporine levels. An increased rate of infection is a common problem, however, and has been associated with "over-immunosuppression" early after transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG induction therapy could be performed without increasing the risk of graft loss by rejection and whether reductions in infection rates and costs are possible. METHODS: Between March 1999 and December 2002, T-cell-adapted ATG induction therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub-populations were screened daily using flow cytometry. If total lymphocytes were <100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+) <50/microl (reference >500/microl) and T-suppressor cells (CD8+) <50/microl (reference >300/microl), then no ATG was given. Further immunosuppression was continued with triple therapy consisting of methylprednisolone, azathioprine and cyclosporine. An historic group of heart transplant recipients given a full-dose ATG regimen for 8 days served as controls. These recipients were treated with ATG (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of >300 mg/dl. Additional immunosuppressive treatment did not differ. Patients in both groups received systemic antibiotics (Imipenem) peri-operatively. Results of routine endomyocardial biopsies and rates of infections were examined. RESULTS: Study group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group, mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p < 0.05) for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the study group compared with 13% in the control group. Rate of deep sternal infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs 1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade >2 were treated successfully with 1,000 mg of methylprednisolone intravenously for 3 days. Both groups showed a similar 1-year survival rate (study 88%, control 89%). CONCLUSIONS: T-cell-adapted ATG induction therapy can be a helpful tool for individualized immunosuppression. It is not associated with an increased rate of rejection. Lower doses of immunosuppression help to minimize the rates of infection. In addition, cytolytic induction therapy combined with reduced ATG results in significant cost reduction.

Adult↗

Cardiovascular and respiratory responses during musical mood induction.

Music is used to induce moods in experimental settings as well as for therapeutic purposes. Prior studies suggest that subjects listening to certain types of music experience strong moods and show physiological responses associated with the induced emotions. We hypothesized that cardiovascular and respiratory patterns could discriminate moods induced via music. 18 healthy subjects listened to 12 music clips, four each to induce happiness, sadness, and fear, while cardiovascular and respiratory responses were recorded using an electrocardiogram and chest strain-gauge belt. After each clip subjects completed a questionnaire. Subjects consistently reported experiencing the targeted mood, suggesting successful mood induction. Cardiovascular activity was measured by calculating time domain measures and heart rate changes during each clip. Respiratory activity was measured by total, inspiration, and expiration lengths as well as changes in mean respiration rate during each clip. Evaluation of individuals' patterns and mixed-model analyses were performed. Contrary to expectations, the time domain measures of subjects' cardiovascular responses did not vary significantly between the induced moods, although a heart rate deceleration was found during the sadness inductions and acceleration during the fear inductions. The time domain respiratory measures varied with clip type: the mean breath length was longest for the sad induction, intermediate during fear, and shortest during the happiness induction. However, analysis using normalized least mean squares adaptive filters to measure time correlation indicated that much of this difference may be attributable to entrainment of respiration to characteristics of the music which varied between the stimuli. Our findings point to the difficulty in detecting psychophysiological correlates of mood induction, and further suggest that part of this difficulty may arise from failure to differentiate it from tempo-related contributions when music is used as the inducer.

Adult↗

Adenomatous polyposis coli influences micronuclei induction by PhIP and acrylamide in mouse erythrocytes.

Micronucleus (MN) induction in erythrocytes of multiple intestinal neoplasia (Min) mice with heterozygous Apc mutation was measured after s.c. injections of acrylamide, glycidamide, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and colchicine, and compared with wild-type (wt) mice. Since Apc influences microtubule dynamics, we wanted to test whether Min-mice were more sensitive to the production of MN than wild-type mice. We also examined the effect of pre-treatment with cytosine beta-D-arabinofuranoside (Ara C) and hydroxyurea, which inhibit ligation of DNA strand breaks in the repair of DNA adducts. All compounds induced a significant increase in MN in both strains of mice with the following potencies: acrylamide<glycidamide<PhIP. No difference in the induction of MN was seen between Min-mice and wt-mice exposed to acrylamide, glycidamide or colchicine without pre-treatment. However, in Min-mice, PhIP treatment induced much less MN than in wt-mice, with about four- and six-fold increase in MN in Min-mice and wt-mice, respectively. A reduced ability to repair PhIP adducts may be the reason for the lower induction of MN in Min-mice. Treatment with Ara C and hydroxyurea, to increase sensitivity, gave more than a four-fold increase in MN, but strongly reduced proliferation. Pre-treatment with Ara C and hydroxyurea made the Min-mice slightly more sensitive to MN induction by glycidamide compared to wt-mice. We conclude that Min-mice are less sensitive than wt-mice to MN induction by PhIP that forms bulky DNA adducts, while Min-mice and wt-mice are equally sensitive to MN induction by acrylamide and glycidamide that form DNA base adducts.

Acrylamide↗

Induction and expression mechanisms of postsynaptic NMDA receptor-independent homosynaptic long-term depression.

The induction of long-term depression (LTD) can be divided into two main forms, one dependent upon activation of postsynaptic NMDAR, and another independent of postsynaptic NMDAR. Non-postsynaptic NMDAR-LTD (non-NMDAR-LTD) occurs in many regions of the brain, and encompasses a wide variety of induction and expression mechanisms. In this article, the induction and expression mechanisms of such LTD in over 10 brain regions are described, with a number of common mechanisms compared across a large range of types of LTD. The article describes the involvement of different presynaptic or postsynaptic receptors in the induction of non-NMDAR-LTD, especially metabotropic glutamate receptors, cannabinoid receptors and dopamine receptors. An increase in presynaptic or postsynaptic intracellular Ca concentration is a key event in induction, commonly followed by activation of certain kinases, especially PKC, p38 MAPK and ERK. Expression mechanisms are either presynaptic via a reduction in release probability, or postsynaptic involving a decrease in AMPAR via phosphorylation of a glutamate receptor subunit, especially GluR2, followed by clathrin-mediated endocytosis. Retrograde signalling from postsynaptic to presynaptic occurs when induction is postsynaptic and expression is presynaptic.

Animals↗

Substance P mediates AP-1 induction in A549 cells via reactive oxygen species.

A common feature in asthma is the induction of reactive oxygen species (ROS) and the AP-1 transcription factor during the inflammatory process. AP-1 induction leads to an increased expression of pro-inflammatory cytokines. Also, higher levels of the pro-inflammatory neuropeptide substance P (SP) have been reported in bronchoalveolar-lavage fluid of asthmatics. Here, the role of SP on ROS induction and the downstream activation of AP-1 in A549 airway epithelial cells was investigated by dichloroflourescein-diacetate method and reporter gene assays. The SP-mediated AP-1 induction was dependent on extracellular calcium and ROS. The likely source of ROS are the mitochondria as rotenone inhibited AP-1 induction and the p47phox subunit of the NADPH oxidase complex, responsible for ROS generation in phagocytotic cells, was not expressed in A549 cells assayed by RT-PCR. This is consistent with results obtained from cells of murine bronchial epithelium, isolated by laser capture microdissection. In summary, this study provides evidence for an SP-mediated induction of AP-1, which may contribute to the expression of pro-inflammatory cytokines.

Calcium↗

Neural crest induction by the canonical Wnt pathway can be dissociated from anterior-posterior neural patterning in Xenopus.

While Wnt signaling is known to be involved in early steps of neural crest development, the mechanism remains unclear. Because Wnt signaling is able to posteriorize anterior neural tissues, neural crest induction by Wnts has been proposed to be an indirect consequence of posteriorization of neural tissues rather than a direct effect of Wnt signaling. To address the relationship between posteriorization and neural crest induction by Wnt signaling, we have used gain of function and loss of function approaches in Xenopus to modulate the level of Wnt signaling at multiple points in the pathway. We find that modulating the level of Wnt signaling allows separation of neural crest induction from the effects of Wnts on anterior-posterior neural patterning. We also find that activation of Wnt signaling induces ectopic neural crest in the anterior region without posteriorizing anterior neural tissues. In addition, Wnt signaling induces neural crest when its posteriorizing activity is blocked by inhibition of FGF signaling in neuralized explants. Finally, depletion of beta-catenin confirms that the canonical Wnt pathway is required for initial neural crest induction. While these observations do not exclude a role for posteriorizing signals in neural crest induction, our data, together with previous observations, strongly suggest that canonical Wnt signaling plays an essential and direct role in neural crest induction.

Animals↗

Tissues and signals involved in the induction of placodal Six1 expression in Xenopus laevis.

Ectodermal placodes, from which many cranial sense organs and ganglia develop, arise from a common placodal primordium defined by Six1 expression. Here, we analyse placodal Six1 induction in Xenopus using microinjections and tissue grafts. We show that placodal Six1 induction occurs during neural plate and neural fold stages. Grafts of anterior neural plate but not grafts of cranial dorsolateral endomesoderm induce Six1 ectopically in belly ectoderm, suggesting that only the neural plate is sufficient for inducing Six1 in ectoderm. However, extirpation of either anterior neural plate or of cranial dorsolateral endomesoderm abolishes placodal Six1 expression indicating that both tissues are required for its induction. Elevating BMP-levels blocks placodal Six1 induction, whereas ectopic sources of BMP inhibitors expand placodal Six1 expression without inducing Six1 ectopically. This suggests that BMP inhibition is necessary but needs to cooperate with additional factors for Six1 induction. We show that FGF8, which is expressed in the anterior neural plate, can strongly induce ectopic Six1 in ventral ectoderm when combined with BMP inhibitors. In contrast, FGF8 knockdown abolishes placodal Six1 expression. This suggests that FGF8 is necessary and together with BMP inhibitors sufficient to induce placodal Six1 expression in cranial ectoderm, implicating FGF8 as a central component in generic placode induction.

Animals↗

PP2A:B56epsilon is required for eye induction and eye field separation.

Eye induction and eye field separation are the earliest events during vertebrate eye development. Both of these processes occur much earlier than the formation of optic vesicles. The insulin-like growth factor (IGF) pathway appears to be essential for eye induction, yet it remains unclear how IGF downstream pathways are involved in eye induction. As a consequence of eye induction, a single eye anlage is specified in the anterior neural plate. Subsequently, this single eye anlage is divided into two symmetric eye fields in response to Sonic Hedgehog (Shh) secreted from the prechordal mesoderm. Here, we report that B56epsilon regulatory subunit of protein phosphatase 2A (PP2A) is involved in Xenopus eye induction and subsequent eye field separation. We provide evidence that B56epsilon is required for the IGF/PI3K/Akt pathway and that interfering with the PI3K/Akt pathway inhibits eye induction. In addition, we show that B56epsilon regulates the Hedgehog (Hh) pathway during eye field separation. Thus, B56epsilon is involved in multiple signaling pathways and plays critical roles during early development.

Animals↗