An attractive explanation for the impairment of long-term contextual memory after strong training in Paip2a−/− mice is excessive activity-induced translation in the absence of PAIP2A. It is conceivable that partial reduction of PAIP2A, as in Paip2a+/− mice, might have a smaller effect on translation and thus lead to a salubrious effect on memory.

Reduction in the PAIP2A protein levels in Paip2a+/− mice was confirmed by western blotting ( Figure 3A). It is striking that, while similar freezing was observed 1 hr after strong contextual training, it was enhanced 24 hr after training in Paip2a+/− relative to WT mice ( Figures 3B and 3C). These data are consistent with the idea that complete removal of PAIP2A might cause memory impairment via excessive translation in response to strong training. In accordance with these results, L-LTP elicited by TBS was not impaired in Paip2a+/− relative to WT hippocampal Trichostatin A in vitro slices ( Figure 3D). Because adult neurogenesis contributes to fear memory extinction (Pan et al., 2012), which is impaired in Paip2a−/− mice, we examined neurogenesis in WT, Paip2a−/−, and Paip2a+/− mice.

Progenitor cell proliferation within the subgranular zone of the dentate gyrus was assessed using systemic injection of BrdU followed by immunostaining or by staining for Ki-67, a marker of proliferating progenitor cells. It is surprising that the number of BrdU- and Ki-67-positive cells was reduced in Paip2a−/− but not in Paip2a+/− mice as compared to WT mice ( Figure S4A), suggesting that impaired memory BMS-354825 ic50 extinction in Paip2a−/− of mice might result from reduced adult neurogenesis.

We also examined the memory phenotype of Paip2b−/− mice, although PAIP2B expression in the brain is lower than PAIP2A ( Berlanga et al., 2006). No differences were found in contextual fear conditioning task between Paip2b−/− mice and their WT littermates 1 hr and 24 hr after training ( Figures S4B and S4C, respectively), suggesting that PAIP2B is not involved in translational regulation of learning and memory. Next, it was pertinent to determine whether PAIP2A is controlled in an activity-dependent manner. No phosphorylation of PAIP2A has been reported. However, PAIP2A levels are homeostatically controlled by proteasome-mediated degradation upon PABP depletion in cell cultures (Yoshida et al., 2006). Therefore, cultured neurons were depolarized with KCl for 5 min to study the effect on PAIP2A levels. PAIP2A protein levels decreased to 69.6% ± 3.3% of baseline 1 min after KCl-induced depolarization and were further reduced to 59.3% ± 4.0% after 10 min. PAIP2A levels returned to normal after 30 min (Figure 4A). Similarly, activation of NMDA receptors with NMDA resulted in the reduction of PAIP2A to 71.8% ± 2.2% of prestimulation levels (Figure 4B). We reasoned that the rapid downregulation of PAIP2A is mediated by proteolytic activity.

01 ± 0.1 SD, p = 0.73, t test). Following this, the latency correlation between spontaneous and evoked activity increases with time during stimulation (three points in the shaded area in Figure 2G, middle inset; mean slope = 0.11 ± 0.12 SD, p = 0.01). Once stimulation ceased, latency correlations decayed gradually (Figure 2G, right inset; mean slope = −0.07 ± 0.08 SD, p = 0.01; see Figure S4A

for the same analyses with higher temporal GSI-IX research buy resolution). Interestingly, this slow decrease in reactivation after stimulation is consistent with data from behaving animals, in which most reactivation is observed only within a few minutes after tasks (Euston et al.,

2007). To quantify the significance of sequence reverberation, we compared averaged values of latency correlations before and after stimulation. The values of latency correlation were significantly higher after stimulation only for S1 in the amphetamine condition (p < 0.0001; t test) but were not significantly different for the urethane-only condition (p > 0.1). Thus, in anesthetized rats injected with amphetamine that induced brain state desynchronization, sensory stimulation caused a gradual reorganization of spontaneous activity patterns in S1, and the “memory” of that stimulation persisted in the following spontaneous activity patterns. As an additional test that stimulus-evoked patterns in S1 are replayed during the following spontaneous activity, we used template-matching

analysis as described in studies with Selleck Ibrutinib behaving animals (Euston et al., 2007 and Tatsuno et al., 2006; see Supplemental Experimental Procedures). Templates for each data set consisted of average stimulus-triggered activity from 0 to 200 ms after stimulus onset. Figures 3A–3C show template, sample raster plots, and template-matching scores for spontaneous activity before and after stimulation for a representative rat. We found that, others in the amphetamine condition (but not the urethane only condition), the number of spontaneous patterns that closely matched the template was higher in the period following tactile stimulation (Figures 3D and 3E; pampth = 0.02, pureth = 0.52; t test). As compared to the results obtained using the latency measure, reverberation disappeared faster after stimulation when analyzed with template matching (Figure S4B). Although it is difficult to pinpoint the exact reason for this discrepancy, tests on simulated data suggest that latency measure could be more robust in small signal-to-noise regimes and less affected by any time compression of replayed patterns, thus giving better estimation of weak and varying reverbatory activity (Figure S2).

6% to 98.1%. On the other hand, the resistance to anthelmintic drugs becomes a serious problem in countries with small ruminants industry (Thomaz-Soccol

et al., 2004 and Vieira et al., 1992). In present study, there was not an EPG decrease in the Moxidectin 0.2% group, even being given every 30 days. In sheep raised in Brazil, H. contortus is the main parasite involved in cases of Moxidectin resistance ( Thomaz-Soccol et al., 2004 and Silva et al., 2008). These results are consistent to the previously reported, with a possible resistance to moxidectin. However, the authors suggest the association of biological control with chemical control, which could help in reducing of helminth infections. In the coprocultures, there was a predominance of Strongyloides sp. in the first quarter, probably due to the goats being young, with a mean age of 8 months, being more susceptible to infection by this gender. In the second quarter, there was selleck compound the predominance of Haemonchus sp., corroborating with Araújo et al. (2007), who observed a greater percentage of this gender in goat feces in a semi-arid region of Ceará, Brazil. Due to the high rainfall in April and May, there was a rise in

the EPG caused by the humidity’s increase, which contributed to a higher re-infection in animals. In the same period, there was a decrease in the PCV. Therefore, all animals in the Control group and five animals in the Moxidectin 0.2% group required salvage de-worming during this period. D. flagrans was able to prevent Crizotinib supplier re-infection, where only one animal required salvage de-worming.

It was observed that the D. flagrans group increased 65% in weight, the Moxidectin 0.2% group increased 38% and the Control group had a 9% of reduction in weight. Chandrawathani et al. (2004) observed that the sheep greater weight Mannose-binding protein-associated serine protease gain in Malaysia occurred in the group receiving. D. flagrans. On the other hand, Silva et al. (2009) found no statistical difference (p > 0.05) in the weight of D. flagrans group and the Control group. The PCV of D. flagrans group were higher than the other groups throughout the experiment, demonstrating that this group had a better physiological response against gastrointestinal parasitism. These results disagree with Silva et al. (2010), who observed that the PCV of sheep receiving D. flagrans was slightly lower than the other groups. In the leukocyte counts, changes were observed due to the occurrence of bacterial diseases of respiratory origin which affected all the animals in the experiment, explaining chronic leukocytosis with neutrophilia. The animals were affected mainly in April and May, the rainy season, where the relative humidity was high. To avoid possible interference in the anthelmintic treatment, no antibiotic treatments were performed, explaining the persistence of changes in the exams until the month of July, when the rainfall and relative humidity had already decreased, allowing the animals to overcome the infection. D.

The glial nature of these cells was confirmed a century later by the use of electron microscopy and GFAP immunohistochemistry (Levitt and Rakic, 1980 and Rakic, 1972). More specifically, in the macaque fetal forebrain, radial glial shafts have ultrastructurally distinct composition, including an abundance of GFAP and a difference in cytoplasmic density from the adjacent migrating neurons. In addition, they have this website numerous lamellate expansions that protrude at right angles from

the main shaft that terminates with one to several endfeet at the pial surface. The studies in primates have led to the concept that these elongated processes of fetal glial cells that span the thickness of the convoluted primate cerebrum serve as guides for migrating neurons (see Rakic, 1988 for review).The molecular characteristics, basic cell shape,

and radial orientation in structures ranging from the spinal cord to the large primate cerebrum have inspired the name “radial glial cells” (RGCs) because it includes the term “glia,” favored by the old literature, as well as the term “radial,” which refers to their basic www.selleckchem.com/products/gdc-0068.html orientation and connection between ventricular and pial surface, but avoids the term “fetal,” since they are not confined to the prenatal period (Rakic, 1972 and Schmechel and Rakic, 1979b). This name has been generally accepted for all vertebrate species (Parnavelas and Nadarajah, 2001) in spite of the substantial species-specific differences in the timing of their transformation from the neuroepithelial cells (Kriegstein and Parnavelas, 2003, Kriegstein and Parnavelas, 2006, Rakic, 2003a and Rakic, 2003b). For example, in primates, some GFAP-positive RGCs appear during early embryonic development (Choi, 1986, deAzevedo et al., 2003, Gadisseux and Evrard, 1985, Kadhim et al., 1988, Levitt et al., 1981, Levitt and Rakic, 1980, Rakic, 1972, Schmechel and Rakic, 1979b, Sidman and Rakic, 1973 and Zecevic, 2004), and a subpopulation stop dividing transiently (Schmechel and Rakic, 1979a) to provide stable scaffolding

for the formation of the large and convoluted cortex (Rakic and Zecevic, 2003a and Rakic and Zecevic, 2003b). The introduction of the Parvulin new term “neural stem cell” about two decades ago and development of advanced methods to study cell lineages in vivo (Gage et al., 1995) and in vitro (Lendahl et al., 1990, Reynolds and Weiss, 1992 and Temple, 1989) transformed the field and led to an unprecedented level of expectation that NSCs might be used to replace virtually any type of neuron lost from neurodegenerative disorders and brain trauma (e.g., Clarke et al., 2000 and Horner and Gage, 2000). Since this time, NSC research has also given us new insights into the regulation of cell division and programmed cell death, both of which determine neuron number.

, 1995). Most current studies have been focused on understanding how the expression of the ecdysone receptor, EcR-B1, is regulated by TGF-β signaling pathway, the cohesin complex, and the Ftz-F1/Hr39 pathway during MB axon pruning ( Figure 8E; Boulanger et al., 2011, Pauli et al., 2008, Schuldiner et al., 2008 and Zheng et al., 2003). However, very little is known about how activation of EcR-B1 downstream effectors is regulated during pruning. It is also unknown whether and how specific intrinsic epigenetic factors cooperate with the extrinsic

ecdysone signal to regulate RAD001 nmr their common downstream target gene activation during pruning. Among 81 epigenetic factors, we isolated the Brm chromatin remodeler and the histone modifier CBP. We demonstrate essential roles of Brm-mediated chromatin remodeling and CBP-mediated histone acetylation in governing dendrite pruning of ddaC neurons in response to ecdysone. We also show that sox14 is a major downstream target gene of both Brm and CBP during ddaC dendrite pruning, because Brm and CBP specifically activate the key ecdysone early-response gene sox14, but not the ecdysone receptor gene EcR-B1 ( Figure 8E). Furthermore, the intrinsic HAT activity of CBP is required for sox14 expression and ddaC dendrite pruning. Our biochemical

analyses reveal that the liganded EcR-B1 forms a protein complex with CBP, which is facilitated by Brm. EcR-B1 and Brm act in conjunction with CBP to coordinately facilitate the local enrichment of Afatinib ic50 an active chromatin mark H3K27Ac at the sox14 gene region, thereby activating their common target sox14 expression. This study provides mechanistic insight into crotamiton how specific intrinsic epigenetic machinery transduces extrinsic hormonal signals to establish a transcriptionally active chromatin state and thereby activate specific transcriptional cascades during remodeling and maturation of the nervous systems in animals. Emerging evidence indicates that ATP-dependent chromatin remodelers play essential roles in the development of the vertebrate nervous system (Yoo and Crabtree,

2009), for example, dendrite outgrowth of hippocampal neurons and self-renewal/differentiation of neural stem cells in mammals (Lessard et al., 2007 and Wu et al., 2007). In Drosophila, RNAi knockdown of brm in embryonic class I ddaD/E neurons exhibited a dendrite misrouting phenotype, suggesting its potential involvement in embryonic dendrite development ( Parrish et al., 2006). Mutations in the Brm complex components revealed dendrite targeting phenotypes in Drosophila olfactory projection neurons ( Tea and Luo, 2011). However, we found that Brm is not important for dendrite development in class IV ddaC neurons because loss of brm function did not affect their dendritic outgrowth and morphology. Rather, we demonstrate a crucial role of the Brm-containing chromatin remodeler in regulating ddaC dendrite pruning during early metamorphosis.

, 2007). Consistent with this, inhibitory inputs mostly contact the dendritic shaft, and one observes sublinear summation when neighboring inhibitory inputs are integrated by pyramidal neurons, or when neighboring excitatory inputs are received by aspiny neurons ( Tamás et al., 2002). Spiny check details dendrites can also integrate inputs in a non-linear regime. Local dendritic spikes (also known

as “calcium spikes,” “calcium plateaus,” or “NMDA spikes”) are generated by focal stimulation of a dendrite (Holthoff et al., 2004, Polsky et al., 2009, Schiller et al., 2000 and Yuste et al., 1994). With two-photon uncaging, linear summation is observed when up to 30 neighboring spines are stimulated, although, if more inputs are stimulated, local spikes are triggered (Losonczy and Magee, 2006). A dendritic spike is a nonlinear phenomenon that bypasses the “synaptic democracy” and prevents the integration of additional inputs. But dendritic spikes could also significantly enrich the computational repertoire of the neuron, enabling the functional association of local inputs (Mel, 1994). Also, dendritic spikes, like the ones that occur in the distal apical dendrite Ulixertinib research buy of neocortical pyramidal neurons,

could enable the amplification of distant inputs that would otherwise not be transmitted to the soma (Larkum et al., 2009 and Yuste et al., 1994). Other functions of these local spikes could be to generate either intrinsic firing patterns (Elaagouby and Yuste, 1999) or persistent activity by the neuron (Major et al., 2008). Finally, local dendritic spikes can generate a strong form of LTD (Holthoff et al., 2004) that could be used as a “punishing signal” to prevent input association and, paradoxically, help preserve linear integration. But regardless of the presence or absence of local dendritic spikes, the neuron still has to solve the conductance shunting problem that arises with simultaneous activation of inputs. Given that, in vivo, dendrites are probably bombarded

with hundreds or perhaps even thousands of active inputs at any given time, if excitatory inputs were located on dendritic shafts, dendrites could be essentially Etomidate short-circuited all the time, making it impossible for voltage signals, including local dendritic spikes, to propagate along. The neuron would also be more reliable if its dendritic integration and signaling were constant under different conditions of synaptic inputs. For all of these reasons, it appears advantageous for the neuron to protect itself from the large conductance changes associated with synaptic transmission, and electrically isolating excitatory inputs into spines could be a solution to this problem. Spines could use neck filtering to ensure a nonsaturating regime of integration and fully exploit the benefits of a distributed input connectivity and, in addition, make dendritic integration more reliable and less dependent on the amount of synaptic activity present.

After recovery, this rabies virus was amplified as efficiently as the SADΔG-GFP rabies virus (10.2

kb genome). While in our hands neither the transgene expressed nor the size of the viral genome prevented production of high-titer ΔG rabies viruses, it is likely that the utility of these viruses will depend on the skill and care taken by those who grow them as well as careful adherence to the established http://www.selleckchem.com/products/AZD2281(Olaparib).html protocols we have developed. One of the main goals of systems neuroscience is to understand the architecture and function of neural circuits. Understanding how neural circuits function will require resolving the connectivity of the components; correlating the function of components with their connectivity; manipulating the activity of selected components and monitoring the activity of other components within the networks; and finally, assessing

the behavioral outcome. Techniques for achieving these goals, however, are limited. The rabies tools we have described here provide many new opportunities to allow the combination of rabies-virus-based circuit tracing with functional studies. For example, expression of the calcium sensor GCaMP3 in neurons that have been infected as a result of their connectivity with specific cell types or a single neuron selleck products could allow observations of direct correlations between connectivity and function in a single living preparation. Here we have explicitly demonstrated this type of approach

by combining retrograde infection with GCaMP3-expressing ΔG rabies virus with in vivo two-photon imaging of visual responses. This allowed measurements of the visual receptive fields of a specific subset of mouse V1 neurons selected on the basis of their connectivity to area AL. Similarly, expression of ChR2 and AlstR should allow control of neural activities in vitro and in vivo and facilitate tests of the causal relationships between connectivity and function within defined neural circuits. It should also be possible to test possible ADAMTS5 postsynaptic targets of connectionally-targeted rabies-virus-infected neurons for functional connectivity with potential postsynaptic neurons through intracellular recording combined with photoactivation of axons from neurons expressing ChR2 from the rabies genome (Petreanu et al., 2007). Targeting infection and transsynaptic labeling with GCaMP3-ΔG, ChR2-ΔG, and AlstR-ΔG rabies in defined cell types or single cells with retrograde infection (Stepien et al., 2010, Wickersham et al., 2007a, Wickersham et al., 2007b and Yonehara et al., 2011), Cre-dependent TVA transduction (Haubensak et al., 2010 and Wall et al., 2010), bridge proteins with TVB (Choi et al., 2010), or single cell electroporation of TVA (Marshel et al., 2010 and Rancz et al., 2011) will be extremely useful for functional studies of identified neural circuits.

Clutch engagement provides the mechanical resistance that is needed for the actin network to overcome the rearward current of retrograde flow, which in turn allows the plasma membrane to translocate forward. Forces www.selleckchem.com/products/torin-1.html generated by clutch resistance of the F-actin network are transmitted

back to the adhesions, resulting in increased surface traction (Aratyn-Schaus and Gardel, 2010, Brown et al., 2006, Giannone et al., 2009 and Hu et al., 2007). Compelling evidence of the clutch model has been demonstrated in neurons (Bard et al., 2008 and Chan and Odde, 2008). In nascent protrusions that result from clutch engagement, newly polymerized actin primes and positions integrins for activation (Chan and Odde, 2008). Adhesions experiencing increased force undergo higher component turnover (Wolfenson et al., 2011). Together, these create a cycle promoting dynamic fluctuation and positive growth. It is clear that mechanical signaling plays an important role in outgrowth and guidance, but its exact mechanism of controlling overall movement has not yet been determined. Adhesions are dynamic complexes whose turnover is critical for cell movement (Huttenlocher and Horwitz, 2011). Stable adhesions immobilize the cell while lack of adhesion makes it incapable of crawling on a substrate. In a motile growth cone, adhesions assemble and

disassemble to change in number, size, and position Y-27632 supplier (Myers and Gomez, 2011 and Thoumine, 2008). Additionally, the individual adhesion components, including the surface receptors, undergo turnover within the point contacts (Dequidt et al., 2007). Adhesions are protein structures in constant flux, ready

to immediately respond to internal and external signals. Modification of adhesion dynamics can effect overall migration or, if done locally within the growth cone, cause a directional guidance response (Myers and Gomez, 2011, Myers et al., 2011 and Woo and Gomez, 2006). Several traditional signaling pathways that work through focal adhesions have been shown to mediate both attractive and repulsive guidance responses. There are numerous almost reviews that are specifically dedicated to the vast signaling networks that work through adhesions (Kamiguchi, 2007, Kolodkin and Tessier-Lavigne, 2011, Maness and Schachner, 2007 and Myers et al., 2011). In this section, we would like to focus on focal adhesion kinase (FAK), a single, well-studied adhesion protein, to highlight how its complex regulation can induce polar effects in the migrating growth cone. We hope to demonstrate the need to understand the spatiotemporal regulation of adhesive contacts. Focal adhesion kinase (FAK) is a protein-tyrosine kinase that provides a direct link between adhesions and intracellular signaling pathways (Mitra et al., 2005 and Parsons, 2003). FAK is downstream of both extracellular matrix and intracellular signaling components, therefore it is in a position to transduce signals to and from adhesions.

However, the precise mechanisms employed by DA to mediate these effects remain largely unknown owing to the multiplicity and complexity of its actions. DA signaling involves a plethora of molecules including kinases, phosphatases, transcription factors, ion channels, and membrane receptors. Moreover, DA’s actions have largely defied interpretation because they vary greatly between cell types, depend on the strength and duration of receptor stimulation, are influenced by current and past cellular states, and compete with other neuromodulatory systems impinging on similar pathways. Thus, despite extensive investigation, there is no unified view of dopamine’s actions in

the CNS, and many studies VX-770 in vivo have yielded contradictory conclusions. Here, we discuss dopamine’s ability to rapidly influence synaptic transmission, dendritic integration, and membrane excitability. The search for neurons that produce DA started in the early 1960s, after the remarkable finding that catecholamine-containing neurons could be visualized in tissue after chemical conversion of CAs into fluorescent molecules with formaldehyde (Carlsson et al., 1962; Falck

et al., 1982). Using this method, seventeen groups of CA cells (designated A1–A17) were initially identified in the CNS. Specific identification of DA-producing cells is complex even with modern techniques. Firmly establishing a dopaminergic identity necessitates the analysis of multiple cellular markers and ideally the demonstration of stimulus-evoked DA release from genetically defined neurons such as by combining optogenetics and carbon fiber voltammetry (e.g., www.selleckchem.com/products/17-AAG(Geldanamycin).html Stuber et al., 2010; Tecuapetla et al., 2010). Collectively, the available data support the existence of ten DA-producing nuclei in the mammalian brain (A8–A17). Neurons within each field can differ significantly with respect to axonal projection areas, electrophysiological properties, and the expression of synthetic enzymes, membrane and vesicular transporters, aminophylline neuropeptides, and other amino acid transmitters (Björklund

and Dunnett, 2007; Hnasko et al., 2010; Lammel et al., 2011). Midbrain DA neurons in the substantia nigra pars compacta (SNc; field A9) and ventral tegmental area (VTA; field A10) are perhaps the best studied of these because of their central roles in the pathology of PD and in reward signaling and reinforcement, respectively. These two centers provide the bulk of DA to the basal ganglia and forebrain and contain the vast majority of DA neurons in the CNS. In the rat, VTA and SNc each contain ∼20,000 neurons bilaterally (German and Manaye, 1993). Given their small numbers and powerful impact on many aspects of behavior, each midbrain DA neuron must exert influence over large brain areas and many cells. Indeed, individual SNc neurons extend impressive axons of half a meter in total length that densely ramify throughout up to 1 mm3 of tissue (Matsuda et al., 2009).

To elevate muscle NT3 expression, we took advantage of mice in which NT3 is overexpressed in skeletal muscle under the control of a myosin light chain (mlc1) promoter

( Taylor et al., 2001). In wild-type mice, muscle-targeted expression of an NT3 transgene resulted in a 2.3-fold increase in pSN number (from ∼230 pSNs/DRG in wild-type mice to ∼540 pSNs/DRG in mlc1NT3 mice) ( Figures 7A and 7B). In L5 DRG the number of pSNs increased by 1.4-fold (from ∼550 in wild-type to ∼810 pSNs/DRG in mlc1NT3 mice) ( Figures 7A and 7B). These NT3-mediated increases in pSN number in L2 and L5 DRG were quantitatively similar to increases observed in Bax1−/− mice ( Figure S4), consistent with the idea that enhanced NT3 signaling prevents the apoptotic death of pSNs. SAHA HDAC order In NT3 heterozygous mice the number of L2 pSNs was reduced by ∼70% of wild-type values, but in L5 DRG the reduction was only ∼55%

( Figure 7C). Thus, the L2 pSN population is more sensitive to elevating learn more or reducing peripheral NT3 levels than their L5 pSN counterparts. We next examined how an elevation of muscle NT3 expression impacts L2 and L5 pSN number in Etv1 mutants. Expression of the mlc1NT3 transgene in Etv1 mutants increased the number of L2 pSNs 2.1-fold, and the number of L5 pSNs 1.4-fold, elevations almost identical to those observed in wild-type mice ( Figures 7A and 7B). In addition, muscle expression of the mlc1NT3 transgene largely restored intraspinal axonal trajectories of pSNs supplying axial, hypaxial, and limb muscles ( Figure 5C; see also Li et al., 2006). More specifically, we determined whether elevation of NT3 expression in Etv1 mutants is able to restore through pSN innervation of muscles that express low levels of NT3. Assessing the status of sensory innervation of body wall, intercostal, and gluteus muscle in Etv1−/−;mlc1NT3

mice revealed vGluT1+ SSEs in all three muscles ( Figure 7D, data not shown). Morphologically the “restored” spindles were highly disorganized, however, and often extended much of the length of the intrafusal muscle fiber ( Figure 7D). Nevertheless, these results further support a view in which NT3, and its muscle-by-muscle variation in expression level, sets the status of Etv1-dependence for pSNs. The diversification of pSNs into discrete functional subclasses drives the assembly of spinal sensory-motor circuits, but the elemental units of sensory diversity and their molecular origins have remained obscure. We report here that developing pSNs destined to innervate different muscle targets exhibit a marked variability in dependence on the ETS transcription factor Etv1, both for survival and differentiation.