The concentration of pepsin (MP Biomedicals, Ohio, USA) used in t

The concentration of pepsin (MP Biomedicals, Ohio, USA) used in the present study was 1% (w/v) and the concentration of HCl was 1% (v/v). Citric acid was added at 8 concentrations from 1% to 20% (w/v) (1, 3, 5, 7, 9, 13, 15, and 20%). The digestive capacity

of ADSs containing varying concentrations click here of citric acid were compared with ADS containing 1% HCl. The fish meat used in the study (mullet) were purchased from a market (Noryangjin, Seoul). Tissue samples were prepared by slicing the fish meat to produce 2 cm2 (about 20 g), and these were placed in 50 ml conical tubes with 40 ml of the ADS samples. The tubes were incubated at 37 °C in a shaking incubator for 1–2 h. To determine digestive capacity of each solution, the concentrations of proteins released from digested samples were measured using a Nanodrop 2000 spectrometer (Thermo Scientific, Wilmington, Delaware, USA) at 280 nm. To investigate the effect of citric acid on parasite survival, M. yokogawai, a fish-borne intestinal trematode

parasite, SP600125 chemical structure was collected from sweetfish, Plecoglossus altivelis, captured from a stream in an endemic area in Gyeongsangbuk-do ( Pyo et al., 2013). The sweetfish were finely ground, mixed with ADSs, incubated at 37 °C for 1–2 h, filtered through a mesh (pore size 1 mm × 1 mm), and washed with 0.85% saline repeatedly until clear. The sediment was carefully observed

under a stereomicroscope. Metagonimus metacercariae were identified morphologically and collected ( Pyo et al., 2013). The metacercariae of M. yokogawai were examined for the effects of ADSs on parasite survival. Metacercariae were incubated at 37 °C with each ADS, and surviving metacercariae were counted under an optical microscope (CHS-213E; Olympus, Tokyo) at 2 h intervals during the 8 h incubation period. The survivability of metacercariae was confirmed by their morphological characteristics. A metacercaria was considered dead if it did not move for 5 min at 25–37 °C with loss of the body wall integrity and faintness of the excretory bladder with few excretory granules. The conventional composition of ADS contains 0.5–1% Adenosine of pepsin and 0.8–1% of HCl with a pH of 1.5–2.0. The addition of citric acid instead of HCl acidified the pepsin solution (Fig. 1). The pH of the pepsin solution itself was 3.76, and the addition of 1% HCl decreased the pH to less than 2.0. The addition of 1% citric acid decreased the pH to 2.44, and the addition of citric acid at concentrations greater than 5% decreased the pH to less than 2.0. ADSs containing citric acid between 5% and 20% resulted in pH values between 1.5 and 2.0 (Fig. 1). These findings show that citric acid concentration needs to be greater than 5% to achieve maximal pepsin activity.

) Thus, wild felids and domesticated cats may spread T gondii o

). Thus, wild felids and domesticated cats may spread T. gondii oocysts in the environment. A cat may excrete millions of oocysts and oocysts can remain viable at 15–35 °C from 32 days to about a year ( Dubey, 2010). The climate in the region is tropical humid, favoring the viability of oocysts. The Amazon River dolphin feeds on fish ( Best and da Silva, 1993) and many of these fishes feed on shellfish. Although T. gondii does not multiply in cold blooded animals aquatic invertebrates and fish can be transport host

at T. gondii oocysts ( Lindsay et al., 2001, Arkush et al., 2003, Miller et al., 2008, Esmerini et al., 2010 and Massie et al., 2010). I. geoffrensis live in rivers where there is a significant seasonal variation in water level, with check details annual average amplitude of 10.6 m ( Ramalho et al., 2009). The seasonal variation in water levels directly influences the habitat distribution and density of botos ( Martin and da Silva, 2004a). Variations in the density

of botos PD0332991 are substantially due to fish migration, dictated by changes in water level and concentrations of dissolved oxygen. These dolphins use preferably occupy the margins of main rivers, streams and lakes ( Martin and da Silva, 2004a). None of the cities or riverside communities of the region have a sewage treatment system, facilitating the contact of these animals with the polluted waters, especially during the dry season when the water level is low and animals are more concentrated. During floods, dolphins are scattered in areas of flooded forests ( Martin and da Silva, 2004b), which can become infected by oocysts from feces of wild cats living in the Reserve. The Amazon River dolphin is a long-lived animal at the top of the food chain, and is therefore a sentinel of environmental contamination (Lailson-Brito et al., 2008). The species inescapably lives in close proximity to man, and consumes some of the same food. The results suggest a possible contamination by T. gondii oocysts in the aquatic environment where these animals live. We thank the interns

of Projeto Boto for their help in capture of animals, collection and analysis of data and the fisherman team for their dedication and care and handling the animals. This paper Astemizole is part of the collaboration agreement between Instituto Nacional de Pesquisas da Amazônia/MCT and Instituto de Desenvolvimento Sustentável Mamirauá-OS/MCT. We gratefully acknowledge funding from Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), Instituto Nacional de Pesquisas da Amazônia (INPA) and Petrobrás Ambiental. “
“The authors regret that there were errors in the ELISA percentages in Table 1, which required correction of the results presented in Table 2, and Table 3 and the model. The corrections appear as follows.

, 2011) At the cellular level, expression of DISC1 is developmen

, 2011). At the cellular level, expression of DISC1 is developmentally regulated within the nervous system (Miyoshi et al., 2003) and DISC1 in turn regulates multiple processes of both embryonic and adult neurogenesis (Christian et al., 2010). At the molecular level, a large number of potential DISC1 binding partners have been identified from a yeast two-hybrid screen (Chubb et al., 2008), many of which are also involved in neurodevelopmental processes implicated in the pathophysiology of psychiatric diseases. Regarded Vemurafenib mw as an “edge piece” of psychiatric genetics, DISC1 may thus provide an entry point to understand molecular mechanisms and etiology underlying

complex psychiatric disorders. Using a combinatorial approach to analyze the effect of genetic manipulations on individual neurons in the animal model, biochemical interactions of endogenous proteins in a homogenous cell population, and genetic associations

in clinical cohorts, we demonstrate two parallel pathways for FEZ1 and NDEL1 that independently cooperate with DISC1 to regulate different aspects of CX-5461 neuronal development and risk for schizophrenia. In the dentate gyrus of the hippocampus, a region implicated in schizophrenia pathophysiology (Harrison, 2004), neurogenesis continues throughout life in all mammals and contributes to specific brain functions (Zhao et al., 2008). Adult hippocampal neurogenesis provides a unique model system for dissecting signaling mechanisms that regulate neurodevelopment and

offers several distinct advantages for molecular analysis, including a prolonged developmental time course for more precise temporal resolution, a single neuronal subtype, Digestive enzyme and amenability to birth-dating, lineage tracing, and genetic manipulations (Christian et al., 2010). Using this in vivo model system, we have identified novel functions of FEZ1 in regulating dendritic growth and soma size of newborn dentate granule cells in the adult hippocampus (Figure 1). Furthermore, results from concomitant suppression of DISC1 and FEZ1 support a synergistic interaction between these two proteins in regulating dendritic growth in vivo (Figure 3). In parallel, the NDEL1-DISC1 interaction regulates a complementary subset of developmental processes, namely, neuronal positioning and development of primary dendrites (Duan et al., 2007). Interestingly, there is no apparent synergistic interaction between FEZ1 and NDEL1 in regulating neuronal development (Figure 4) and no protein-protein interaction in the absence of DISC1 (Figure 5). These results illustrate two discrete pathways associated with the DISC1 interactome that, in conjunction, account for most of the DISC1-mediated effects in orchestrating development of newborn neurons during adult hippocampal neurogenesis (Table 1).

Furthermore, cumulative adversity is associated with smaller gray

Furthermore, cumulative adversity is associated with smaller gray matter (GM) volume in medial prefrontal, anterior cingulated, and insula (Ansell et al., 2012). Moreover, chaos in the family and living environment is associated with impaired self-regulatory behaviors along with elevated blood pressure and signs of obesity in childhood (Evans et al., 2005 and Evans and Wachs, 2010) and major life events in early adolescence are linked to impaired

self-control that reflects, at least in part, impaired prefrontal cortical development (Duckworth et al., 2012). Moreover, in a study using CX-5461 datasheet a Childhood Trauma Questionnaire and MRI imaging of the brain (Edmiston et al., 2011), AZD6244 price adverse childhood experiences correlated negatively with gray matter volume in prefrontal cortex, striatum, amygdala, sensory association cortices, and cerebellum. In particular, physical abuse, physical neglect, and emotional neglect were associated with rostral prefrontal gray matter reductions and decreases in dorsolateral and orbitofrontal cortices, insula, and ventral striatum were associated with physical abuse, while decreases in cerebellum were associated with physical neglect and decreases in dorsolateral, orbitofrontal, and subgenual

prefrontal cortices, striatum, amygdala, hippocampus, and cerebellum were associated with emotional neglect (Edmiston et al., 2011). There

were sex differences in that decreases in the emotional regulation regions, including prefrontal cortex, were associated with childhood trauma in girls, while reductions in caudate GM volume, a brain region related to impulse control, were seen in boys (Edmiston et al., 2011). There Dipeptidyl peptidase are important sex differences both in how early life stressors affect the prefrontal cortex development and in connectivity with other brain regions involved in cognitive function and emotional regulation. Prenatal stress caused sexually dimorphic, opposite changes in synaptic connectivity in response to the same experience, and both male and female offspring demonstrated a loss of neuron number and estimated synapse number in the hippocampus despite exhibiting increased spine density (Mychasiuk et al., 2012). Prenatal stress also led to a sex-specific pattern of dendrite structure that was manifested during adolescence in prenatally stressed males, but not females, which became evident later in adulthood (Markham et al., 2012). Yet, in studies of chronic juvenile stress (Eiland et al., 2012), the absence of qualitative sex differences in morphological and behavioral responses to chronic stress from postnatal days 20–41 speaks to the important role of the onset of puberty and the role of circulating gonadal hormones in conferring sex differences in response to stressors.

The present papers, however, by examining rigorously the cell bio

The present papers, however, by examining rigorously the cell biology of these mutations and the CAP-Gly domain itself have opened doors to further understanding retrograde movement and stress the importance of maintaining a finely tuned axonal transport system. “
“Studies of cortical plasticity have classically focused on glutamatergic, excitatory synaptic changes. A large fraction of the excitatory synapses in the neocortex are impinging on dendritic spines.

This allows researchers to monitor the formation and elimination of excitatory synapses by watching BMS-387032 molecular weight the appearance and disappearance of fluorescently labeled dendritic spines in live neurons. Similarly, large glutamatergic axonal varicosities

are often used as anatomical surrogates for vesicular presynaptic boutons. The turnover of these structures occurs throughout life even in virtually naive animals, and newly added synapses stably integrate into cortical circuits upon changes in experience or learning (Fu et al., 2012, Hofer et al., 2009 and Holtmaat and Svoboda, 2009). Similar to their excitatory counterparts, inhibitory synapses are thought to display continuous structural changes. Synaptic inhibition in the neocortex is governed by a diverse group of interneurons that transmit GABA or glycine in spatially and temporally discrete manners (Markram et al., 2004). Inhibitory inputs can modulate excitatory neuronal membrane potentials, enforce unless spike timing, and effectively restrain the summation Autophagy pathway inhibitor of postsynaptic excitatory

potentials (Isaacson and Scanziani, 2011). Therefore, regulated inhibition through the formation and elimination of synapses could efficiently leverage excitatory activity and hence cortical network processing or plasticity. Studies of inhibitory synapse dynamics on excitatory cells have been complicated due to the lack of postsynaptic anatomical proxies that can be resolved by light microscopy. Recent time-lapse imaging studies in vivo have described experience-dependent and structural remodeling of GABAergic interneuron axonal boutons, suggesting that some excitatory cells are subject to changes in inhibitory synaptic input (Chen et al., 2011 and Keck et al., 2011). However, from these studies it is difficult to deduce the identity let alone the dendritic compartments of the postsynaptic cells that may be affected. In this issue of Neuron, Chen et al. (2012) and van Versendaal et al. (2012) present an elegant method for studying inhibitory synapse dynamics in excitatory cells in vivo based on fluorescently tagged gephyrin. This synaptic scaffolding protein is highly enriched in GABAergic and glycinergic postsynaptic compartments, and when expressed in neurons, fluorescent puncta can be observed, which are likely to represent inhibitory synapses ( Moss and Smart, 2001).

(2012) exist in the reward circuit, it would provide not only a p

(2012) exist in the reward circuit, it would provide not only a potential mechanism for the “ghrelinergic” effects on reward but also a new paradigm for the rational development of therapeutic interventions for abnormal reward-seeking behaviors. “
“A major goal of neuroscience is to elucidate the molecular mechanisms mediating the different forms and phases of long-term synaptic plasticity that are thought to underlie learning and memory. Although many forms of synaptic plasticity have been described, four have been the most widely studied: (1) NMDA receptor (NMDAR)-dependent, transient early long-term potentiation (LTP), (2) NMDAR-dependent, persistent late LTP that requires Palbociclib in vitro new protein synthesis, (3) mGluR-dependent

long-term depression (LTD) that also requires new synthesis, and (4) NMDAR-dependent LTD. A current challenge to the field is to determine how these four forms of plasticity might mediate different aspects of behavior in the hopes of finding simple rules that may reframe the psychology of memory in neurophysiological and molecular terms. This requires understanding the core molecular mechanisms of these long-term synaptic modifications

in detail. The molecular mechanisms for any long-term form of synaptic plasticity can be divided into three phases: induction, triggering the plasticity; maintenance, sustaining it over time; and expression, transducing the mechanism of maintenance into a change HSP signaling pathway in synaptic transmission. From the point of view of the search for the physical substrates of memory, the heart of the matter is maintenance. In recent years, significant progress has been made toward understanding the maintenance

of the two protein synthesis-dependent forms of synaptic plasticity. Whereas induction involves scores of signaling molecules, the critical requirement for new protein synthesis in the transition to maintenance constrains the complexity of the signaling network involved in sustaining modified synaptic new transmission in the maintenance phase. For example, in late LTP, PKMζ, a protein kinase C isoform that is uniquely synthesized as an autonomously active kinase by strong afferent stimulation, is the only kinase that has been found to maintain increases in synaptic transmission from hours to days after induction ( Sacktor, 2011). Because PKMζ is not involved in the maintenance of LTD, pharmacological and genetic tools that inhibit the kinase and block or reverse late LTP have been used to demonstrate a role for late-LTP maintenance in several forms of long-term memory ( Sacktor, 2011). Analogously, researchers are hot on the trail of a few suspects that are newly synthesized in mGluR-LTD, including arc, STEP, and MAP1b, which may maintain this form of synaptic depression ( Lüscher and Huber, 2010). In contrast, the core mechanisms that maintain the forms of synaptic plasticity that rely entirely on posttranslational modifications have been harder to pin down.

A second Gal4 line, E605-Gal4, contains PERin and displays the sa

A second Gal4 line, E605-Gal4, contains PERin and displays the same behavioral phenotypes upon neural inactivation or activation ( Figure S4). These data suggest that there is a reciprocal buy VE-821 balance between feeding initiation and locomotion mediated by PERin activity. To test whether the act of proboscis extension sufficed to inhibit locomotion, we immobilized the proboscis in an extended or retracted position with wax. Wild-type flies with

extended proboscises moved significantly less (Figure 7D), arguing that motor activity or proprioceptive feedback from the proboscis inhibits locomotion. Consistent with this, immobilizing the proboscis in a retracted state partially rescued the locomotor defect of flies with inactivated PERin MK-2206 clinical trial neurons (Figure 7D). Thus, proboscis extension feeds back onto circuits to inhibit locomotion, allowing for mutually exclusive behaviors. Many behaviors are mutually exclusive, with the decision to commit to one behavior excluding the selection of others. Here, we show that feeding initiation and locomotion are mutually

exclusive behaviors and that activity in a single pair of interneurons influences this behavioral choice. PERin neurons are activated by stimulation of mechanosensory neurons and activation of PERin inhibits proboscis extension, suggesting that they inhibit feeding while the animal is walking. Consistent with this, leg removal or immobilization enhances proboscis extension probability and this is inhibited by increased PERin activity. The opposite behavior is elicited upon inhibiting activity in PERin neurons: animals show constitutive proboscis extension at the expense of locomotion. This work shows that activity in a single pair of interneurons dramatically influences the choice between feeding initiation and movement. The precise mechanism MRIP of activation of PERin neurons remains to be determined. PERin dendrites reside in the first leg neuromere, suggesting that they process information from the legs. Stimulation of leg chemosensory bristles with sucrose or quinine or activation of sugar, bitter, or water neurons using

optogenetic approaches did not activate PERin neurons, nor did satiety state change tonic activity. Stimulation of sensory nerves into the ventral nerve cord and stimulation of mechanosensory neurons, using a nompC driver, activated PERin. In addition, by monitoring activity of PERin while flies moved their legs, we demonstrated that activity was coincident with movement. These studies argue that PERin is activated by nongustatory cues in response to movement, likely upon detection of mechanosensory cues. Additional cues may also activate PERin. Studies of behavioral exclusivity in other invertebrate species suggest two mechanisms by which one behavior suppresses others (Kristan and Gillette, 2007). One strategy is by competition between command neurons that activate dedicated circuits for different behaviors.

Thus, we hypothesized that an additional transcription factor cou

Thus, we hypothesized that an additional transcription factor could be primarily required for specifying the PVM cell fate. PVM is located on the left

side of the animal and adjacent to the PVD cell soma (Figure 1). Mutants of zag-1(rh315) ( Wacker et al., 2003) showed an extra PVD-like cell in this location ( Figure 5; Table S2) ( Smith et al., 2010). In addition to displaying the highly branched morphology that is characteristic of PVD, the extra PVD-like cell also expressed multiple PVD markers ( Table S1). We considered the possibility that this PVD-like cell could have arisen from duplication of the PVD lineage ( Figure 1). However, the absence of an additional dat-1::mcherry-expressing PDE neuron in zag-1(rh315) excludes this model (data selleck products not shown). Because the C59 wnt PVD sister cell, V5Rpaapp, normally undergoes programmed cell death ( Figure 1), we entertained the alternative idea that this cell survives in the zag-1 mutant

and gives rise to a duplicate PVD neuron. This idea is ruled out, however, by the finding that the introduction of an egl-1 mutation to prevent V5Rpaapp apoptosis ( Conradt and Horvitz, 1998) results in a third PVD-like cell on the left side in the zag-1; egl-1 double mutant (data not shown). Finally, expression of the light touch neuron-specific marker, mec-4::mCherry, was not detected in this region, therefore suggesting that the normal PVM cell is missing in the zag-1 mutant ( Table S1). Based on these results, we conclude that the extra PVD neuron observed in zag-1 mutants arises from the conversion of PVM into a PVD-like

cell. We refer to this converted PVM cell in zag-1 mutants as cPVM. Similar results were obtained for zag-1(ok214) and zag-1(zd86) ( Clark and Chiu, 2003) (data not shown). Megestrol Acetate The timing at which cPVM initiates lateral branching is also consistent with the proposal that PVM is converted to a PVD-like fate in zag-1 mutants. PVM normally arises soon after hatching in the wild-type animal ( Sulston and Horvitz, 1977) ( Figure 1), and cPVM was initially observed in L1 zag-1 mutant animals. Also, as noted earlier for cAVM, the cPVM cell initiated a PVD-like branching pattern in L2 larvae in zag-1 mutants ( Figure 5C), whereas the PVD neuron, which first appears in L2 animals, does not display lateral branches until later, in the L3 stage ( Smith et al., 2010). We used transgenic animals expressing the mosaic PVD::mCherry marker to distinguish PVD versus cPVM lateral branches in later larval stages and in the adult. Random loss of the mCherry marker from PVD but not cPVM confirmed that the PVD-like branching pattern of the cPVM cell is retained during larval development ( Figure 5) (see Experimental Procedures). This analysis also revealed that PVD (marked with PVD::GFP) showed a reduced number of lateral branches in the posterior region occupied by cPVM in the zag-1 mutant ( Figure 5).

In LRRTM4−/− mice, dentate gyrus granule cells but not CA1 neuron

In LRRTM4−/− mice, dentate gyrus granule cells but not CA1 neurons show reductions in VGlut1 but not GAD65 immunoreactive inputs and in spine density. LRRTM4−/− dentate gyrus granule cells in primary culture show deficits in excitatory synapse density and in activity-induced synaptic recruitment of AMPA receptors. Moreover, loss of LRRTM4 causes a deficit in excitatory synaptic transmission specifically in dentate gyrus granule cells and not CA1 pyramidal neurons in acute brain slice. Loss of LRRTM4 also results in a reduced level of PSD-95 family proteins in dentate Enzalutamide solubility dmso gyrus crude synaptosomes.

Thus, LRRTM4 contributes to excitatory presynapse and postsynapse development. Further, we identify a new family of LRRTM4 ligands, HSPGs,

thus differentiating LRRTM4 from LRRTM1 and LRRTM2, which bind the LNS domain of neurexins. LRRTM4 can directly bind to multiple glypicans and syndecans, and their interaction requires the HS chains. Furthermore, HSPGs are required for presynaptic differentiation induced by LRRTM4, and levels of HSPGs are reduced in the dentate gyrus of LRRTM4−/− mice. Thus, different postsynaptic LRRTM family members function in synapse organization through different presynaptic mechanisms, and the LRRTM4-HSPG complex is particularly important for proper development of glutamatergic synapses on dentate gyrus granule Casein kinase 1 cells. HSPGs have previously been implicated in synapse development and function selleck products (Van Vactor et al., 2006 and Yamaguchi, 2001). Agrin is a well-known synapse-organizing protein at the mammalian neuromuscular junction (Wu et al., 2010), and syndecan and the glypican Dally-like regulate synapse development in different ways at the Drosophila neuromuscular junction ( Johnson et al., 2006). However, the mechanisms of action of HSPGs at central synapses are less well understood. The major HSPGs in the brain are the cell surface GPI-anchored glypicans, the transmembrane

syndecans, and the secreted proteins agrin and perlecan. Syndecan-2 is present at both presynaptic and postsynaptic sites of glutamatergic synapses ( Hsueh et al., 1998), and postsynaptic syndecan-2 regulates dendritic spine development ( Ethell et al., 2001). Glypican-4 and glypican-6 released from glia cells after phospholipase cleavage were recently shown to promote GluA1-containing AMPA receptor surface insertion and functional synapse development in isolated retinal ganglion cells ( Allen et al., 2012). All glypicans are expressed by neurons, thus neuronal glypicans in their cell surface GPI-anchored or cleaved soluble forms may also contribute to synapse development.

This suggests that polarization defects had impeded the radial mi

This suggests that polarization defects had impeded the radial migration of

these neurons. The polarization defects resulting from downregulation of NP1 may depend on the level of NP1-siRNA expression in various progenitor cells. Assuming that the level of EGFP expression correlated with that of NP1-siRNA, we measured the EGFP fluorescence intensity of individual neuronal somata of various morphologies at different cortical layers in E21 rat embryos. The results (Figure 6H) suggest that the level of NP1-siRNA expression correlated well with the severity of the learn more polarization defects, with neurons that exhibited multipolar morphology at the SVZ showing higher levels of GFP expression, in comparison to those exhibiting bipolar morphology

at the IZ and CP (Figure 6Hb). Interestingly, in cells expressing control siRNA, the opposite was found for GFP expression—higher in bipolar cells in the IZ/CP than multipolar cells in the SVZ (Figure 6Ha). The latter finding suggests that for NP1-siRNA expressing neurons, the difference in the level of NP1-siRNA expression between normally migrating bipolar cells and polarization-defective PD0325901 concentration multipolar cells could be even higher than that indicated by the EGFP expression. In this study, we examined the role of Sema3A in polarizing axon/dendrite differentiation in cultured hippocampal neurons and showed that localized exposure of an undifferentiated neurite to Sema3A induces its differentiation into the dendrite, via local suppression of axon development. This suppression is mediated by Sema3A-induced elevation of cGMP/PKG signaling that downregulates cAMP/PKA-dependent LKB1 and GSK-3β Histone demethylase phosphorylation, which is essential for axon formation. In addition to this local axon suppression effect, Sema3A also promotes dendrite

growth. Furthermore, downregulation of Sema3A signaling in developing cortical neurons in vivo resulted in severe polarization defects and reduced length of the leading process, the apical dendrite, in support of the notion that Sema3A may regulate axon/dendrite polarity during the early phase of neuronal development by both suppressing axon-specific cAMP/PKA-dependent processes and promoting dendrite-specific cGMP/PKG-dependent functions. Axon/dendrite differentiation during neuronal polarization is a coordinated process, as exemplified by the formation of a single axon and multiple dendrites in cultured hippocampal neurons (Dotti et al., 1988). In most studies using these cells, the focus has been on the process of axon differentiation, with the implicit assumption that specification of the axon of one neurite determines the fate of all other neurites as dendrites. In this “axon dominance” view, the first event of neuronal polarization is the emergence of a localized signal for axon specification in one neurite.