, 1997), both of the pathways for nitrate reduction to ammonia ar

, 1997), both of the pathways for nitrate reduction to ammonia are expressed only during anaerobic growth. Transcription of narGHJI and

nirBD is also activated by the NarX-NarL two-component regulatory system in response to moderate concentrations of nitrate; nirBD, and to a much lesser extent narGHJI, are also activated by the alternative two-component system, NarQ-NarP (Rabin & Stewart, 1993). Classical genetic approaches and more recent whole genome transcriptomic studies have indicated that the cytoplasmic pathway is physiologically more significant only in nitrate-rich environments that might occur in soil, in some highly contaminated sediments, and waste water treatment plants (Potter et al., 1999). In contrast, the transcription of genes for the periplasmic Nap-Nrf pathway CAL-101 price is activated by NarQ-NarP in response to low concentrations of nitrate (< 100 μM) Maraviroc clinical trial but are repressed by NarX-NarL when nitrate is abundant (Page et al., 1990).

This indicates that the periplasmic pathway confers a selective advantage for bacterial survival in the nitrate limited environment of the gastro-intestinal tract of humans and other warm blooded animals (Potter et al., 1999; Constantinidou et al., 2006). Based upon the accumulation of very small quantities of nitrous oxide during nitrite reduction, it was assumed that the rate of NO production was two to three orders of magnitude slower than the rate of nitrite reduction (Smith, 1983).

It was predicted that NO was a side product released during Tyrosine-protein kinase BLK nitrite reduction by either NirBD or NrfA. However, there is an extensive literature showing that the major source of nitrosative stress is NO generated by the interaction of the cytoplasmic nitrate reductase, NarG, with nitrite (reviewed in the accompanying paper by Vine et al., 2011). Realization that enteric bacteria can reduce nitrite to NO re-opened the question whether NO is generated by a single mechanism or by more than one pathway, depending on the conditions under which the bacteria are grown. Specifically, is more NO generated by the membrane-associated nitrate reductase, NarG, by one of the nitrite reductases, NirBD or NrfAB, or by other molybdoproteins that are active during anaerobic growth? The sensitive response of the transcription repressor, NsrR, to NO provides a method to detect the presence of NO in the bacterial cytoplasm (Hutchings et al., 2000; Corker & Poole, 2003; Bodenmiller & Spiro, 2006; Tucker et al., 2008). By coupling an NsrR-regulated E. coli promoter to lacZ expression during anaerobic growth in the presence of nitrite, it was shown that mutations in nirBD or nrfAB resulted in greater expression of lacZ, indicative of the increased accumulation of NO in the cytoplasm (Vine et al., 2011). Conversely, deletion of the narGHJI operon significantly decreased but did not eliminate lacZ expression, indicative of less accumulation of cytoplasmic NO.

If there is a question about the patient’s capacity to make an in

If there is a question about the patient’s capacity to make an informed decision, this should be assessed using 17-AAG mouse the principles in the Mental Capacity Act 2005 [28]. Patients presenting at the clinic may be at different stages of readiness to take therapy [29] and clinicians’ first task is to assess their readiness, by means of open questions rather than closed, before supporting and furthering patients’ decisions on therapy. However, if a patient presents in circumstances that necessitate starting ART immediately, for example with certain AIDS diagnoses or very low CD4 cell counts, then doctors should prescribe ART and provide support

for the patient’s adherence, especially through the first few weeks. Recognizing symptoms that patients attribute to ART side effects might avoid loss of adherence and deterioration of trust in the patient–provider relationship [30, 31].

A ‘perceptions and practicalities’ approach should be used to tailor support to meet the needs of the individual, to identify both the perceptual factors (such as beliefs about ART) and practical factors (such as capacity and resources) influencing adherence [8,32]. Supporting patients requires good communication not just between clinician and patient but also between all healthcare staff involved with their care, including those in their HIV services, their GP and any clinicians involved in management of co-morbid conditions. Patients should be offered copies of letters about them sent to their GP and other physicians. Sirolimus price The advantages of HIV status disclosure to the patient’s GP should be discussed and considered best practice, as several situations require consensual clinical decision-making. A patient’s decision not to disclose their

status to their GP should, however, always be respected, subject to the clinician’s duty to protect vulnerable individuals. “
“Some fungi cause disease in humans and plants, while others have demonstrable potential for the control of insect pests. Galactosylceramidase In addition, fungi are also a rich reservoir of therapeutic metabolites and industrially useful enzymes. Detailed analysis of fungal biochemistry is now enabled by multiple technologies including protein mass spectrometry, genome and transcriptome sequencing and advances in bioinformatics. Yet, the assignment of function to fungal proteins, encoded either by in silico annotated, or unannotated genes, remains problematic. The purpose of this review is to describe the strategies used by many researchers to reveal protein function in fungi, and more importantly, to consolidate the nomenclature of ‘unknown function protein’ as opposed to ‘hypothetical protein’– once any protein has been identified by protein mass spectrometry.

05) None of the LAB strains stimulated AFB1 accumulation in any

05). None of the LAB strains stimulated AFB1 accumulation in any of the fungal strains assayed. On the contrary, toxin production of A. flavus RC2053 and A. flavus RC2055 was totally inhibited by L. fermentum L23. It is likely that the low concentration of AFB1 in the presence of Lactobacillus strains could

be due to low mycelial biomass formation. Growth inhibition could directly affect AFB1 production as a result of low synthesis of the enzymes involved. Furthermore, AFB1 is a secondary metabolite that does not occur during primary growth of fungus, so that growth inhibition may reduce its production. In this study we have showed that there could exist a relationship between fungal growth and AFB1 production. In fact, these results showed that minimal yields of toxin coincided with PI3K Inhibitor Library minimal mycelial growth. Tukey’s test of the data revealed the influence of L. fermentum L23 and L. rhamnosus L60 on growth parameters (lag phase and growth rate) and AFB1 production. Our results agree with Zinedine PLX3397 cell line et al. (2005), who demonstrated the ability of some strains of LAB to reduce the initial concentration of AFB1 in MRS broth.

Similar observations were made by Aryantha & Lunggani (2007), who observed that L. plantarum, L. fermentum and Lactobacillus delbrueckii significantly inhibited fungal growth of A. flavus and AFB1 production. Dalié et al. (2010) established that the main LAB recognized

for their ability to limit mycotoxinogenic mould growth belong to the genera Lactococcus and Lactobacillus, including L. rhamnosus, in agreement with our results. These results reflect a strong ability to inhibit growth rate and AFB1 production by both Lactobacillus strains with a wide spectrum of antimicrobial activity and high probiotic potential. This suggest that the use of LAB with antifungal properties instead of chemical preservatives would enable the food and feed industry to produce organic food without chemical additives. In addition to the known excellent properties of Lactobacillus strains, they could enhance Orotic acid the nutritional value and prolong the conservation of food. These results are important given that these aflatoxicogenic fungi are natural contaminants of raw materials used for food and feed production, which could be effectively controlled by L. rhamnosus L60 and L. fermentum L23, both strains having probiotic properties. It is concluded that, under favourable conditions, the two lactobacilli strains not only inhibited aflatoxicogenic fungal growth, but also inhibited AFB1 biosynthesis. Future studies with L. rhamnosus L60 and L. fermentum L23 may test the application of these lactobacilli as biocontrollers of fungal contaminants and also to extend the self life of food and feed stuffs, approaching in situ their probiotic properties.

Patient baseline characteristics are summarized in

Table

Patient baseline characteristics are summarized in

Table 1. Six women were receiving ART prior to pregnancy. The median (range) time on treatment until the first antepartum pharmacokinetic sampling in these subjects was 125 (23–236) weeks. Five patients were receiving LPV/r-based therapy, whereas one patient initially received nelfinavir but switched to LPV/r at 30 weeks’ gestation as a result of the withdrawal of nelfinavir from the market at this Selleck BIBF 1120 time. Five of the six women had an undetectable pVL at baseline. Forty women (17 treatment-naïve, 16 treatment-experienced and seven of unknown treatment status) initiated LPV/r therapy in pregnancy. All took LPV for at least 2 weeks prior to the first TDM. The median (range) gestational age at the time of treatment initiation in these patients was 25 (15–36) weeks. Forty-four

patients (96%) at baseline were prescribed the LPV/r tablet at the standard dose of 400/100 mg twice daily. However, one patient received four tablets (800/200 mg) once daily and another initially received LPV/r, underwent TDM in the second trimester, but was later (at 28 weeks’ gestation) switched to boosted atazanavir because of nausea. The NRTI backbone was primarily zidovudine+lamivudine (Combivir, GlaxoSmithKline, London, UK) in 41 (89%) patients. LPV (total and unbound) and RTV (total) trough concentrations were determined in three patients in the first trimester, 13 in the second [for the purpose of subsequent statistical analysis pharmacokinetic data from the first and second buy Fluorouracil trimesters were combined (n=16), as presented

in Table 2] and 43 patients in the third trimester. Median (range) gestational age at the time of pharmacokinetic sampling was 8 (8–11) weeks in the first trimester, 24 (17–29) weeks in the second trimester and 31 (26–40) weeks in the third trimester. In addition, 12 patients had measurements taken postpartum. Median (range) follow-up time after delivery was 8 (5–12) weeks. At the time nearest to delivery, 32 patients (70%) had undetectable pVL, eight patients Pregnenolone (17%) had detectable pVL [median (range) 80 (56–418) copies/mL] and six patients (13%) were unavailable (two were lost to follow-up, two were transferred to another maternity unit, one had a miscarriage, and one result was not applicable). Eight subjects had pVL measurements taken in conjunction with pharmacokinetic sampling postpartum; all were undetectable. Thirty-one patients (67%) achieved pVL <50 copies/mL at a median (range) of 11 (2–33) weeks. Six patients (13%) had undetectable pVL pre-pregnancy, five of whom were on ART prior to conception. Fourteen patients (30%) remained on ART postpartum for their own health. There were 42 live births (one set of twins) and one miscarriage in the cohort; the remaining four patients transferred to another maternity unit. Of the 42 live births, 27 (64%) were born by spontaneous vaginal delivery (SVD) and 15 (36%) by caesarean section (four elective; 11 emergency).

coli control (Fig 5, lane 4) Twenty-five years after its charac

coli control (Fig. 5, lane 4). Twenty-five years after its characterization as an obligate intracellular Alphaproteobacteria (Fryer et al., 1992), it has only recently been demonstrated that P. salmonis Epacadostat is truly a free-living bacterial pathogen, belonging to the Gammaproteobacteria group (Fryer & Hedrick, 2003). The bacteria is known to survive in either fresh (Graggero et al., 1995) or marine waters (Olivares & Marshall, 2010) and moreover it is also known

to be highly adaptable when exposed to limiting and/or stressing conditions, which mimics its natural situation in the oceans (Rojas et al., 2008). Additionally, the presence of insertion sequences and putatively other mobile genetic elements in P. salmonis represents a solid evidence that the adaptability potential of the bacteria resides in its versatile genome (Marshall et al., 2011). In this context, the description of a TA locus in P. salmonis appears to be a natural consequence of this versatility. Indeed, TA loci are conserved (often in multiple copies) in the genomes of many organisms that can cause persistent infections and/or persist in the environment: M. tuberculosis, Helicobacter pylori, Coxiella burnetii, Leptospira interrogans, Vibrio cholerae, Ceritinib mouse and Salmonella

enterica serovars Typhi and Typhimurium, as well as Haemophilus influenzae, are good examples of this fact (Daines et al., 2007). Additionally, it is important to consider that TA loci are highly abundant in free-living bacteria, but

lost from host-associated microorganisms (Pandey & Gerdes, 2005). To date, nine TA families have been reported in the literature: VapBC, RelE, ParE, MAzF, Doc, HipA, HigB, CcdB, and ω-ɛ-ζ (Van Melderen & Saavedra De Bast, 2009). The VapBC is the largest family of bacterial TA modules, representing close to 40% of all the TA loci known, and grouped together by virtue of their toxin components, in most cases belong to the PilT N-terminal domain family of proteins, which in turn function as ribonucleases (Cooper et al., 2009; Robson et al., 2009). Thus, it appears logical and important to identify TA loci in emerging 2-hydroxyphytanoyl-CoA lyase prokaryotic organisms in order to improve our understanding of these systems, and more broadly, in attempting to understand the cellular mechanisms behind bacterial adaptation (Sevin & Barloy-Hubler, 2007). We have characterized a new and functional bicistronic operon that encodes the two genes of a Type II TA module in P. salmonis. The organization of the P. salmonis TA locus shows many characteristics of other bacterial TA modules. The presence of IRs in the promoter region (Fig. 1) is a feature that is present in various Type II TA systems, such as the vapBC and ChpK operons of L. interrogans (Picardeau et al., 2001; Zhang et al., 2004). The localization of the antitoxin gene upstream of the toxin ORF is a distinctive feature shared by all Type II TA loci homologous to the P. salmonis system. The P.

Here, b is the y-intercept and m is the slope To study the effec

Here, b is the y-intercept and m is the slope. To study the effects of time-on-task and task difficulty on microsaccades, we analysed the slopes of the linear fits of the data from the peak velocity–magnitude relationship slope per block (Di Stasi et al., 2013a,b). Microsaccade rates,

microsaccade magnitudes and peak velocity–magnitude relationship slopes met the assumption of normality (Kolmogorov–Smirnov test, all P-values > 0.05). For each of these variables we performed a 2 × 6 repeated-measures anova with the experimental condition (Easy vs. Difficult) and time-on-task Seliciclib (blocks 1–6) as the within-subjects factors. Microsaccade directions, number of fixation breaks, and blink rates were not normally distributed, so we used non-parametric analyses for these variables

(Friedman’s test and Wilcoxon’s matched paired tests). We determined the effect of task difficulty during mental arithmetic on microsaccade dynamics. Participants performed one Control task (fixation only) and two types of mental arithmetic tasks (Easy and Difficult) over six consecutive time blocks, during a single experimental session. Task performance and subjective ratings are commonly used to assess task difficulty (Di Stasi et al., 2013a,b; Gao et al., 2013). Here, both task performance (Fig. 3) and subjective ratings (Table 1) data indicated a successful manipulation of task difficulty. The Difficult task generated less correct answers and lower numbers of mental calculation http://www.selleckchem.com/products/bmn-673.html steps than the Easy task (Fig. 3), and the Difficult task led to higher levels of perceived difficulty (F1,8 = 19.40, 3-oxoacyl-(acyl-carrier-protein) reductase P < 0.001; MSE = 1.98) and lower levels of happiness (F1,8 = 6.75, P < 0.05; MSE = 2.41) than the Easy task (Table 1). Time-on-task affected the number of mental calculation steps. The number of mental calculation steps increased linearly with time-on-task in both mental arithmetic conditions, indicating an improvement in performance throughout the session (Fig. 3, right panel), presumably due to practice. Time-on-task did not affect subjective ratings (all F-values < 3; Table 2). Microsaccade rate was lower for the Difficult task than

for the Easy task (Figs 4A and S1; Table 1), and increased linearly with time-on-task in both conditions. There was no significant interaction between task difficulty and time-on-task (Fig. 4A; Table 2). Microsaccade rates in the Control (i.e. fixation only) condition were consistent with those reported in previous research (Martinez-Conde et al., 2009, 2013). Microsaccade magnitude was higher for the Difficult task than for the Easy task (Fig. 4B; Table 1), and did not change with time-on-task in either condition. There was no significant interaction between task difficulty and time-on-task (Fig. 4B inset; Table 2). Microsaccade magnitudes in the Control (i.e. fixation only) condition were consistent with those reported in previous studies (Martinez-Conde et al., 2009, 2013).

SraG is an sRNA found in several enterobacterial species, but its

SraG is an sRNA found in several enterobacterial species, but its targets have not been characterized.

Here, we compared the protein expression patterns between the wild-type and an sraG-depleted mutant of Yersinia pseudotuberculosis by proteomic analysis. Sixteen proteins were up- or downregulated, and the negative regulatory role of SraG associated with the YPK_1206-1205 operon was confirmed. A region in the coding sequence of YPK_1206 was further demonstrated to be required for this negative regulation. Post-transcriptional regulation by small non-coding RNAs (sRNAs) in bacteria is recognized as an important Buparlisib mw regulatory mechanism capable of modulating a wide range of cellular processes and physiological responses (Toledo-Arana et al., 2007; Görke & Vogel, 2008). To date, over 100 sRNAs have been identified in Escherichia coli (Waters & Storz, 2009). Most chromosome-encoded sRNAs are found to be

trans-encoded sRNAs (Waters & Storz, 2009), which directly interact with their target mRNAs to influence the translation initiation and/or mRNA stability (Brantl, 2009), and a short complementary region of about 7–9 bp is commonly required for sRNA–mRNA interaction (Gottesman, 2004; Papenfort et al., 2010). Although increasing numbers of sRNAs have been identified in different bacteria, the roles of most remain unknown. SraG is one such sRNA, first reported in E. coli by a computational approach and then verified by Northern blotting (Argaman et al., 2001). Determination of the 5′ and 3′ ends revealed that the sraG BAY 80-6946 mw gene is located between pnp (polynucleotide phosphorylase, PNPase) and rpsO (30S ribosomal

protein S15) in E. coli and transcribes divergently with pnp and convergently with rpsO (Argaman et al., 2001). SraG transcripts increase in logarithmic phase, peak in late-logarithmic phase and disappear in late-stationary phase, and are activated by heat and cold shock treatments (Argaman et al., 2001). Sequence analysis demonstrated that sraG also exists in several other enteric bacteria, e.g. Salmonella, Shigella, Klebsiella and Yersinia (Hershberg et al., 2003; Sridhar et al., 2009), and the intergenic location of sraG in these bacteria is the same as reported in E. coli (Sridhar et al., PAK5 2009). In Listeria monocytogenes, an sRNA gene named rliD is also located between pnpA and rpsO in a similar way to sraG, although their DNA sequences do not share high similarity (Mandin et al., 2007). In this study, we characterized the regulatory targets of SraG in Yersinia pseudotuberculosis. We applied proteomic analysis to compare the global protein expression pattern of wild-type (WT) with an isogenic sraG deletion mutant. Expression levels of 16 proteins were changed more than 1.5-fold in the sraG mutant strain. Of these potential targets, the regulatory role of SraG to YPK_1206-1205 operon was further investigated.


“Proteorhodopsins (PRs), light-driven proton pumps, consti


“Proteorhodopsins (PRs), light-driven proton pumps, constitute the largest family of the microbial rhodopsins. PRs are widely distributed in the oceanic environment and freshwater, but no bacteria with PRs have been isolated from freshwater so far. To facilitate isolation of the bacteria with PR genes, we constructed

Etoposide a vector system that can be used to clone potential PR genes and render color changes when overexpressed in Escherichia coli. Using this method, we successfully isolated a strain with PR gene from freshwater and identified it as Exiguobacterium sp. JL-3. The full length PR gene was then cloned using the SEFA PCR method. Protein sequence alignment showed that JL-3_PR shares high sequence identity (84–89%) with the PRs from Exiguobacterium strains, but low sequence identity (< 38%) with other PRs. Surprisingly, we could not detect any proton-pumping activity in the native JL-3 cells and protoplasts, but the recombinant JL-3_PR do pump protons when overexpressed in E. coli. Sequence analysis further revealed that the PRs from Exiguobacterium had an unusual lysine as the proton donor instead of the typical acidic residue. These data suggest that JL-3_PR is a sensory PR rather than a proton pump. "
“Pseudomonas aeruginosa

are known to have a wide physiological potential allowing them to constantly populate diverse environments leading to severe infections of humans such as septicemia, leg ulcers, and burn wounds. We set out to probe physiological characteristics of P. aeruginosa isolates from diabetic Venetoclax datasheet leg ulcers collected from Helsinki metropolitan area. A total of 61 clinical isolates were obtained. Detailed phenotypic (physiological) characteristics [outer membrane (OM) permeability, membrane voltage, and activity of multidrug

resistance pumps] were determined in several growth phases leading to the division of the analyzed set of P. aeruginosa strains into five distinct clusters including 3-mercaptopyruvate sulfurtransferase cells with similar physiological properties. In addition, their antibiotic resistance patterns and genetic heterogeneity were determined. Multiple isolates from the same patient were genetically very closely related and belonged to the same phenotypic cluster. However, genetically close isolates from different patients expressed very different phenotypic properties. The characteristics of infected patients seem to determine the growth environments for microorganisms that adapt by changing their physiological and/or genetic properties. “
“Cysteine synthase A encoded by cysK catalyzes the synthesis of cysteine from O-acetylserine. Expression of cysK in Escherichia coli is under the control of CysB, a LysR family transcription factor. Herein we showed that the expression of cysK is regulated by several genetic and environmental factors in addition to CysB: two genetic factors, OmpR and CysE, and lithium. Based on the findings, we constructed the high-level expression system of cysK.


“Proteorhodopsins (PRs), light-driven proton pumps, consti


“Proteorhodopsins (PRs), light-driven proton pumps, constitute the largest family of the microbial rhodopsins. PRs are widely distributed in the oceanic environment and freshwater, but no bacteria with PRs have been isolated from freshwater so far. To facilitate isolation of the bacteria with PR genes, we constructed

http://www.selleckchem.com/products/nutlin-3a.html a vector system that can be used to clone potential PR genes and render color changes when overexpressed in Escherichia coli. Using this method, we successfully isolated a strain with PR gene from freshwater and identified it as Exiguobacterium sp. JL-3. The full length PR gene was then cloned using the SEFA PCR method. Protein sequence alignment showed that JL-3_PR shares high sequence identity (84–89%) with the PRs from Exiguobacterium strains, but low sequence identity (< 38%) with other PRs. Surprisingly, we could not detect any proton-pumping activity in the native JL-3 cells and protoplasts, but the recombinant JL-3_PR do pump protons when overexpressed in E. coli. Sequence analysis further revealed that the PRs from Exiguobacterium had an unusual lysine as the proton donor instead of the typical acidic residue. These data suggest that JL-3_PR is a sensory PR rather than a proton pump. "
“Pseudomonas aeruginosa

are known to have a wide physiological potential allowing them to constantly populate diverse environments leading to severe infections of humans such as septicemia, leg ulcers, and burn wounds. We set out to probe physiological characteristics of P. aeruginosa isolates from diabetic Venetoclax price leg ulcers collected from Helsinki metropolitan area. A total of 61 clinical isolates were obtained. Detailed phenotypic (physiological) characteristics [outer membrane (OM) permeability, membrane voltage, and activity of multidrug

resistance pumps] were determined in several growth phases leading to the division of the analyzed set of P. aeruginosa strains into five distinct clusters including Bay 11-7085 cells with similar physiological properties. In addition, their antibiotic resistance patterns and genetic heterogeneity were determined. Multiple isolates from the same patient were genetically very closely related and belonged to the same phenotypic cluster. However, genetically close isolates from different patients expressed very different phenotypic properties. The characteristics of infected patients seem to determine the growth environments for microorganisms that adapt by changing their physiological and/or genetic properties. “
“Cysteine synthase A encoded by cysK catalyzes the synthesis of cysteine from O-acetylserine. Expression of cysK in Escherichia coli is under the control of CysB, a LysR family transcription factor. Herein we showed that the expression of cysK is regulated by several genetic and environmental factors in addition to CysB: two genetic factors, OmpR and CysE, and lithium. Based on the findings, we constructed the high-level expression system of cysK.


“NMDA receptors (NMDARs) form glutamate-gated ion channels


“NMDA receptors (NMDARs) form glutamate-gated ion channels widely expressed in the central nervous system and highly permeable to calcium ions. NMDARs have always attracted much attention because of their central implications in numerous physiological and pathological processes including synaptic

plasticity and excitotoxicity. Ever since the discovery of NMDARs three decades ago, it has been acknowledged that native NMDARs do not form a homogeneous population of receptors but rather exist as multiple subpopulations that differ in their functional properties and, presumably, physiopathological roles. NMDARs are in fact large multi-subunit complexes arranged into heteromeric assemblies composed RG7204 supplier selleck kinase inhibitor of four homologous subunits within a repertoire of over 10 different subunits: eight GluN1 isoforms, four GluN2 subunits (A–D) and two GluN3 subunits (A and B). This review gives an overview of our current knowledge of the molecular basis underlying NMDAR functional heterogeneity. The modular architecture and expression profile of NMDAR subunits together with the basic principles of NMDAR operation are first introduced. The influence of subunit composition on receptor functional properties is then described, with emphasis put on the impact of differential incorporation of GluN1

and GluN2 subunits (the roles of GluN3 subunits being less well understood). The final part presents recent studies revealing the central, and largely unsuspected, role of the extracellular N-terminal Orotidine 5′-phosphate decarboxylase region in generating functional diversity of NMDARs. Indeed, the identity of this region, which is distal to the membrane and precedes the agonist-binding domains, determines key biophysical and pharmacological attributes of the various NMDAR subtypes. “
“Cranial motor neurons, which are divided into somatic motor (SM), branchiomotor (BM) and visceral motor (VM) neurons, form distinct axonal trajectories to innervate their synapse targets. Rho GTPase regulates various neuronal functions through one of the major effector proteins, Rho-kinase. Here, we addressed the in vivo role of the Rho/Rho-kinase

signaling pathway in axon patterning of cranial motor neurons. We performed conditional expression of a dominant-negative mutant for RhoA or Rho-kinase in transgenic mice by using the Cre-loxP system to suppress the activity of these molecules in developing cranial motor neurons. Blockade of the Rho/Rho-kinase signaling pathway caused defects in the patterning of SM axons but not in that of BM/VM axons, in which defects were accompanied by reduced muscle innervation and reduced synapse formation by SM neurons. In addition, blockade of the signaling pathway shifted the trajectory of growing SM axons in explant cultures, whereas it did not appear to affect the rate of spontaneous axonal outgrowth.