Effects of axillary blockade on regional cerebral blood flow during dynamic hand contractions.

Regional cerebral blood flow (rCBF) was measured at orbitomeatal (OM) plane +5.0 and +9.0 cm in 10 subjects at rest and during dynamic hand contractions before and after axillary blockade. Handgrip strength was significantly reduced, and rating of perceived exertion increased after blockade. During hand contractions before blockade, contralateral hemispheric cerebral blood flow (CBF) at OM +9.0 increased from a resting value of 58 (49-75) to 63 (52-82) ml.100 g-1.min-1; contralateral motor sensory rCBF at OM +9 from 58 (50-77) to 71 (64-84); motor sensory rCBF at OM +5 from 67 (54-76) to 77 (64-87) and 70 (62-84) contralaterally and ipsilaterally, respectively; and supplementary motor area (SM) rCBF from 64 (53-69) to 75 (67-88) ml.100 g-1.min-1. During dynamic hand contractions after axillary blockade, CBF did not increase at OM +5 or in the SM. Furthermore, contralateral motor sensory rCBF at OM +9 increased much less. Axillary blockade had no effect on resting CBF, rCBF, or increases in the two during hand contractions of the opposite hand. Thus neural feedback from the contracting muscle is necessary for the increases in SM bilateral OM +5 motor sensory rCBF and the maximal increase in contralateral OM +9 motor sensory rCBF during dynamic hand contractions.     

Spinal nerve segmentation in the chick embryo: analysis of distinct axon-repulsive systems

In higher vertebrates, the segmental organization of peripheral spinal nerves is established by a repulsive mechanism whereby sensory and motor axons are excluded from the posterior half-somite. A number of candidate axon repellents have been suggested to mediate this barrier to axon growth, including Sema3A, Ephrin-B, and peanut agglutinin (PNA)-binding proteins. We have tested the candidacy of these factors in vitro by examining their contribution to the growth cone collapse-inducing activity of somite-derived protein extracts on sensory, motor, and retinal axons. We find that Sema3A is unlikely to play a role in the segmentation of sensory or motor axons and that Ephrin-B may contribute to motor but not sensory axon segmentation. We also provide evidence that the only candidate molecule(s) that induces the growth cone collapse of both sensory and motor axons binds to PNA and is not Sema3A or Ephrin-B. By grafting primary sensory, motor, and quail retinal neurons into the chick trunk in vivo, we provide further evidence that the posterior half-somite represents a universal barrier to growing axons. Taken together, these results suggest that the mechanisms of peripheral nerve segmentation should be considered in terms of repellent molecules in addition to the identified molecules.     

Anterograde Components of Axonal Transport in Motor and Sensory Nerves in Experimental 2,5-Hexanedione Neuropathy

Anterograde slow and fast axonal transport was examined in rats intoxicated with 2,5-hexanedione (1 g/kg/week) for 8 weeks. Distribution of radioactivity was measured in 3-mm segments of the sciatic nerve after labelling of proteins with [35S]methionine or [3H]leucine and glycoproteins with [3H]fucose. The axonal transport of the anterograde slow components was examined after 25 (SCa) and 10 days (SCb), in motor and sensory nerves. SCa showed an increased transport velocity in motor (1.25 +/- 0.08 mm/day versus 1.01 +/- 0.05 mm/day) and in sensory nerves (1.21 +/- 0.13 mm/day versus 1.06 +/- 0.07 mm/day). The relative amount of labelled protein in the SCa wave in both fiber systems was also increased. SCb showed unchanged transport velocity in motor as well as in sensory nerves, whereas the amount of label was decreased in the motor system. Anterograde fast transport in motor nerves was examined after intervals of 3 and 5 h, whereas intervals of 2 and 4 h were used for sensory nerves. Velocities and amounts of labelled proteins of the anterograde fast component remained normal. We suggest that the increase in protein transport in SCa reflects axonal regeneration.     

Normative nerve conductions in the tail of rhesus macaques (Macaca mulatta)

BACKGROUND: The aim of this study was to test the feasibility of using the tail of Macaca mulatta for neurophysiological testing of the peripheral nervous system. METHODS: Motor and sensory nerve conduction studies (NCS) of the tail were obtained by surface stimulation and recording. The technique utilized was novel. Unlike other NCS obtained from other peripheral nerves, this technique did not require any special neurophysiological expertise. RESULTS: The latency of the motor and sensory response was 2.5 +/- 0.71 and 1.1 +/- 0.27 ms respectively. The amplitude of the motor and sensory response was 8.1 +/- 5.1 mV and 14.6 +/- 9.4 microV respectively. Similar to human beings, there was a statistically significant relationship between age and motor amplitude, motor latency and sensory latency. CONCLUSIONS: Based on our results, a relatively simple, reproducible neurophysiological monitoring technique of the peripheral nervous system is possible.     

A quantitative model of the switch cycle of an archaeal flagellar motor and its sensory control

By reverse-engineering we have detected eight kinetic phases of the symmetric switch cycle of the Halobacterium salinarum flagellar motor assembly and identified those steps in the switch cycle that are controlled by sensory rhodopsins during phototaxis. Upon switching the rotational sense, the flagellar motor assembly passes through a stop state from which all subunits synchronously resume rotation in the reverse direction. The assembly then synchronously proceeds through three subsequent functional states of the switch: Refractory, Competent, and Active, from which the rotational sense is switched again. Sensory control of the symmetric switch cycle occurs at two steps in each rotational sense by inversely regulating the probabilities for a change from the Refractory to the Competent and from Competent to the Active rotational mode. We provide a mathematical model for flagellar motor switching and its sensory control, which is able to explain all tested experimental results on spontaneous and light-controlled motor switching, and give a mechanistic explanation based on synchronous conformational transitions of the subunits of the switch complex after reversible dissociation and binding of a response regulator (CheYP). We conclude that the kinetic mechanism of flagellar motor switching and its sensory control is fundamentally different in the archaeon H. salinarum and the bacterium Escherichia coli.     

Cerebral cortical representation of reflexive and volitional swallowing in humans

The purpose of this study was to compare cerebral cortical representation of experimentally induced reflexive swallow with that of volitional swallow. Eight asymptomatic adults (24-27 yr) were studied by a single-trial functional magnetic resonance imaging technique. Reflexive swallowing showed bilateral activity concentrated to the primary sensory/motor regions. Volitional swallowing was represented bilaterally in the insula, prefrontal, cingulate, and parietooccipital regions in addition to the primary sensory/motor cortex. Intrasubject comparison showed that the total volume of activity during volitional swallowing was significantly larger than that activated during reflexive swallows in either hemisphere (P < 0.001). For volitional swallowing, the primary sensory/motor region contained the largest and the insular region the smallest volumes of activation in both hemispheres, and the total activated volume in the right hemisphere was significantly larger compared with the left (P < 0.05). Intersubject comparison showed significant variability in the volume of activity in each of the four volitional swallowing cortical regions. We conclude that reflexive swallow is represented in the primary sensory/motor cortex and that volitional swallow is represented in multiple regions, including the primary sensory/motor cortex, insular, prefrontal/cingulate gyrus, and cuneus and precuneus region. Non-sensory/motor regions activated during volitional swallow may represent swallow-related intent and planning and possibly urge.     

Regulation of afferent transmission in the feeding circuitry of Aplysia

Although feeding in Aplysia is mediated by a central pattern generator (CPG), the activity of this CPG is modified by afferent input. To determine how afferent activity produces the widespread changes in motor programs that are necessary if behavior is to be modified, we have studied two classes of feeding sensory neurons. We have shown that afferent-induced changes in activity are widespread because sensory neurons make a number of synaptic connections. For example, sensory neurons make monosynaptic excitatory connections with feeding motor neurons. Sensori-motor transmission is, however, regulated so that changes in the periphery do not disrupt ongoing activity. This results from the fact that sensory neurons are also electrically coupled to feeding interneurons. During motor programs sensory neurons are, therefore, rhythmically depolarized via central input. These changes in membrane potential profoundly affect sensori-motor transmission. For example, changes in membrane potential alter spike propagation in sensory neurons so that spikes are only actively transmitted to particular output regions when it is behaviorally appropriate. To summarize, afferent activity alters motor output because sensory neurons make direct contact with motor neurons. Sensori-motor transmission is, however, centrally regulated so that changes in the periphery alter motor programs in a phase-dependent manner.     

Effects of octopamine, dopamine, and serotonin on production of flight motor output by thoracic ganglia of Manduca sexta

Effects of biogenic amines on a centrally generated motor pattern in Manduca sexta were examined by pressure injecting nanomole to micromole amounts of octopamine, dopamine or serotonin into thoracic ganglia. Motor output was recorded extracellularly from a pair of antagonistic flight muscles and their motor neurons. The monoamines were found to alter production of a motor pattern that produces rhythmic wing flapping (10 Hz) and exhibits phase relationships similar to those in the flight pattern of intact moths. In mesothoracic ganglia with sensory nerves intact, octopamine (4 X 10(-9) mol) injected into lateral regions evoked regular firing of a single motor neuron, whereas a higher dose (4 X 10(-8) mol) often elicited the flight motor pattern. In the absence of sensory input, these doses of octopamine had little effect. Low doses (10(-10) mol) greatly enhanced motor responses to electrical stimulation of a wing sensory nerve. Dopamine (2 X 10(-10) mol) injected into the medial region of the mesothoracic ganglion elicited the flight motor pattern in the presence or absence of sensory input. Rhythmic output induced by dopamine (5 X 10(-10) mol) was suppressed by injecting serotonin (5 X 10(-10) mol) into the same region. These findings demonstrate that dopamine, octopamine, and serotonin have different effects on motor output in Manduca and suggest that these amines are involved in initiating, maintaining and terminating flight behavior, respectively. Octopamine may elicit flight production by enhancing the efficacy of sensory transmission thereby increasing excitability or arousal. Dopamine may act on interneurons involved in generating the flight motor pattern.     

A widely distributed antigen developmentally regulated in the nervous system

We have identified a glycoprotein (BEN) of 95-100 x 10(3) Mr using a monoclonal antibody. This protein is transiently expressed at the cell surface of the peripherally projecting neurons, i.e. motoneurons of the spinal cord and cranial nuclei, sensory neurons of the dorsal root and cranial sensory ganglia and sympathetic, parasympathetic and enteric neurons. In vitro cultures of dorsal root and sympathetic ganglia have shown that BEN is expressed on neurons but not on glial cells. On motor and sensory neurons, BEN first appears at the level of the cell body just after withdrawal from the cell cycle. Soon afterwards, expression of the antigen extends to the elongating axon. After a few days, BEN is no longer expressed by the motor and sensory neurons, disappearing first from the cell body and then progressively from the fibres. The loss of expression is concomitant with the onset of intense proliferation of satellite and Schwann cells. This modulated expression within the nervous system is unlike that of any surface glycoprotein so far described in vertebrates. Preliminary biochemical analysis indicates that, although it bears the adhesion-associated epitope HNK-1, BEN does not share characteristics with any previously described axonal glycoprotein. Consequently, we speculate that this glycoprotein might be a novel molecule implicated in selective adhesion phenomena, such as axonal fasciculation.     

Different subsets of axonal guidance cues are essential for sensory neurite outgrowth to cutaneous and muscle targets in the dorsal ramus of the embryonic chick

The dorsal ramus nerve diverges dorsally from each spinal nerve to innervate the epaxial muscle and dermis that are derived in situ from each dermamyotome. The outgrowth of both the sensory and motor components of this nerve are sensitive to the proximity of the dermamyotome. Motoneurons display a direct target response that is not dependent upon the concurrent outgrowth of sensory neurites (Tosney: Dev. Biol. 122:540-588, 1987). Likewise, the outgrowth of sensory neurites could be directly dependent on the dermamyotome. Alternatively, sensory neurites could be dependent on motor axons that in turn require the dermamyotome for outgrowth. To distinguish between these possibilities, motor outgrowth was abolished by unilateral ventral neural tube deletion and the patterns of subsequent sensory neurite outgrowth were assessed. The cutaneous nerve branch formed in all cases. In contrast, neither of the epaxial muscle nerves formed in the absence of epaxial motoneuron outgrowth. Furthermore, sensory neurites could not be detected diverging into muscle from the cutaneous nerve or entering muscle via other novel routes. We conclude that motoneurons are essential for sensory outgrowth to epaxial muscle but not to cutaneous targets. It is clear that different subsets of navigational cues guide sensory afferents to muscle and to cutaneous destinations.     

Peripheral glia direct axon guidance across the CNS/PNS transition zone.

CNS glia have integral roles in directing axon migration of both vertebrates and insects. In contrast, very little is known about the roles of PNS glia in axonal pathfinding. In vertebrates and Drosophila, anatomical evidence shows that peripheral glia prefigure the transition zones through which axons migrate into and out of the CNS. Therefore, peripheral glia could guide axons at the transition zone. We used the Drosophila model system to test this hypothesis by ablating peripheral glia early in embryonic neurodevelopment via targeted overexpression of cell death genes grim and ced-3. The effects of peripheral glial loss on sensory and motor neuron development were analyzed. Motor axons initially exit the CNS in abnormal patterns in the absence of peripheral glia. However, they must use other cues within the periphery to find their correct target muscles since early pathfinding errors are largely overcome. When peripheral glia are lost, sensory axons show disrupted migration as they travel centrally. This is not a result of motor neuron defects, as determined by motor/sensory double-labeling experiments. We conclude that peripheral glia prefigure the CNS/PNS transition zone and guide axons as they traverse this region.     

Anatomical coupling of sensory and motor nerve trajectory via axon tracking

It is a long-standing question how developing motor and sensory neuron projections cooperatively form?a common principal grid of peripheral nerve pathways relaying behavioral outputs and somatosensory inputs. Here, we explored this issue through targeted cell lineage and gene manipulation in mouse, combined with in?vitro live axon imaging. In the absence of motor projections, dorsal (epaxial) and ventral (hypaxial) sensory projections form in a randomized manner, while removal of EphA3/4 receptor tyrosine kinases expressed by epaxial motor axons triggers selective failure to form epaxial sensory projections. EphA3/4 act non-cell-autonomously by inducing sensory axons to track along preformed epaxial motor projections. This involves cognate ephrin-A proteins on sensory axons but is independent from EphA3/4 signaling in motor axons proper. Assembly of peripheral nerve pathways thus involves motor axon subtype-specific signals that couple sensory projections to discrete motor pathways.     

Preparation of Aplysia Sensory-motor Neuronal Cell Cultures

The nervous system of the marine mollusk Aplysia californica is relatively simple, consisting of approximately 20,000 neurons. The neurons are large (up to 1 mm in diameter) and identifiable, with distinct sizes, shapes, positions and pigmentations, and the cell bodies are externally exposed in five paired ganglia distributed throughout the body of the animal. These properties have allowed investigators to delineate the circuitry underlying specific behaviors in the animal¹. The monosynaptic connection between sensory and motor neurons is a central component of the gill-withdrawal reflex in the animal, a simple defensive reflex in which the animal withdraws its gill in response to tactile stimulation of the siphon. This reflex undergoes forms of non-associative and associative learning, including sensitization, habituation and classical conditioning. Of particular benefit to the study of synaptic plasticity, the sensory-motor synapse can be reconstituted in culture, where well-characterized stimuli elicit forms of plasticity that have direct correlates in the behavior of the animal^2,3. Specifically, application of serotonin produces a synaptic strengthening that, depending on the application protocol, lasts for minutes (short-term facilitation), hours (intermediate-term facilitation) or days (long-term facilitation). In contrast, application of the peptide transmitter FMRFamide produces a synaptic weakening or depression that, depending on the application protocol, can last from minutes to days (long-term depression). The large size of the neurons allows for repeated sharp electrode recording of synaptic strength over periods of days together with microinjection of expression vectors, siRNAs and other compounds to target specific signaling cascades and molecules and thereby identify the molecular and cell biological steps that underlie the changes in synaptic efficacy.An additional advantage of the Aplysia culture system comes from the fact that the neurons demonstrate synapse-specificity in culture^4,5. Thus, sensory neurons do not form synapses with themselves (autapses) or with other sensory neurons, nor do they form synapses with non-target identified motor neurons in culture. The varicosities, sites of synaptic contact between sensory and motor neurons, are large enough (2-7 microns in diameter) to allow synapse formation (as well as changes in synaptic morphology) with target motor neurons to be studied at the light microscopic level.In this video, we demonstrate each step of preparing sensory-motor neuron cultures, including anesthetizing adult and juvenile Aplysia, dissecting their ganglia, protease digestion of the ganglia, removal of the connective tissue by microdissection, identification of both sensory and motor neurons and removal of each cell type by microdissection, plating of the motor neuron, addition of the sensory neuron and manipulation of the sensory neurite to form contact with the cultured motor neuron.Open in a separate windowClick here to view.^{(105M, flv)}     

Sensory Neurons Do Not Induce Motor Neuron Loss in a Human Stem Cell Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.     

A critical look at the embodied cognition hypothesis and a new proposal for grounding conceptual content.

Many studies have demonstrated that the sensory and motor systems are activated during conceptual processing. Such results have been interpreted as indicating that concepts, and important aspects of cognition more broadly, are embodied. That conclusion does not follow from the empirical evidence. The reason why is that the empirical evidence can equally be accommodated by a 'disembodied' view of conceptual representation that makes explicit assumptions about spreading activation between the conceptual and sensory and motor systems. At the same time, the strong form of the embodied cognition hypothesis is at variance with currently available neuropsychological evidence. We suggest a middle ground between the embodied and disembodied cognition hypotheses--grounding by interaction. This hypothesis combines the view that concepts are, at some level, 'abstract' and 'symbolic', with the idea that sensory and motor information may 'instantiate' online conceptual processing.     

Long-term changes in neurotrophic factor expression in distal nerve stump following denervation and reinnervation with motor or sensory nerve

Several factors have been proposed to account for poor motor recovery after prolonged denervation, including motor neuron cell death and incomplete or poor regeneration of motor fibers into the muscle. Both may result from failure of the muscle and the distal motor nerve stump to continue expression of neurotrophic factors following delayed muscle reinnervation. This study investigated whether regenerating motor or sensory axons modulate distal nerve neurotrophic factor expression. We found that transected distal tibial nerve up-regulated brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, down-regulated neurotrophin-3 and ciliary neurotrophic factor mRNA, and that although these levels returned to normal with regeneration, the chronically denervated distal nerve stump continued to express these neurotrophic factors for at least 6 months following injury. A sensory nerve (the cutaneous saphenous nerve) sutured to distal tibial nerve lowered injury-induced BDNF and GDNF mRNA levels in distal stump, but repair with a mixed nerve (peroneal, containing muscle and cutaneous axons) was more effective. Repair with sensory or mixed nerves did not affect nerve growth factor or neurotrophin-3 expression. Thus, distal nerve contributed to a neurotrophic environment for nerve regeneration for at least 6 months, and sensory nerve repair helped normalize distal nerve neurotrophic factor mRNA expression following denervation. Furthermore, as BDNF and GDNF levels in distal stump increased following denervation and returned to control levels following reinnervation, their levels serve as markers for the status of regeneration by either motor or sensory nerve.     

Establishment of vagal sensorimotor circuits during fetal development in rats

The differentiation of vagal motor neurons and their emerging central relationship with vagal sensory afferents was examined in fetal rats. To identify peripherally projecting sensory and motor neurons, 1,1′-dioctadecyl 3,3,3′,3′-tetramethylindocarbocyanine perchloarate (DiI) was inserted into the proximal gut or cervical vagus nerve in fixed preparations. At embryonic day (E) 12, labeled vagal sensory neurons are present in the nodose ganglia and a few sensory axons project into the dorsolateral medulla. Central sensory processes become increasingly prevalent between E13 and E14 but remain restricted to the solitary tract. Vagal motor neurons are first labeled at E13, clustered within a region corresponding to the nucleus ambiguus (NA). Additional motor neurons appear to be migrating toward the NA from the germinal zone of the fourth ventricle. Motor neurons in the dorsal motor nucleus of the vagus (DMV) first project to the gut at E14 and have processes that remain in physical contact with the ventricular zone through E16. Sensory axons emerge from the solitary tract at E15 and project medially through the region of the nucleus of the solitary tract (NST) to end in the ventricular zone. A possible substrate for direct vagovagal, sensorimotor interaction appears at E16, when vagal sensory fibers arborize within the DMV and DMV dendrites extend into the NST. By E18, the vagal nuclei appear remarkably mature. These data suggest specific and discrete targeting of vagal sensory afferents and motor neuron dendrites in fetal rats and define an orderly sequence of developmental events that precedes the establishment of vagal sensorimotor circuits. © 1993 John Wiley & Sons, Inc.     

Independent development of sensory and motor innervation patterns in embryonic chick hindlimbs

Previous studies suggest that sensory axon outgrowth is guided by motoneurons, which are specified to innervate particular target muscles. Here we present evidence that questions this conclusion. We have used a new approach to assess the pathfinding abilities of bona fide sensory neurons, first by eliminating motoneurons after neural crest cells have coalesced into dorsal root ganglia (DRG) and second by challenging sensory neurons to innervate muscles in a novel environment created by shifting a limb bud rostrally. The resulting sensory innervation patterns mapped with the lipophilic dyes DiI and DiA showed that sensory axons projected robustly to muscles in the absence of motoneurons, if motoneurons were eliminated after DRG formation. Moreover, sensory neurons projected appropriately to their usual target muscles under these conditions. In contrast, following limb shifts, muscle sensory innervation was often derived from inappropriate segments. In this novel environment, sensory neurons tended to make more "mistakes" than motoneurons. Whereas motoneurons tended to innervate their embryologically correct muscles, sensory innervation was more widespread and was generally from more rostral segments than normal. Similar results were obtained when motoneurons were eliminated in embryos with limb shifts. These findings show that sensory neurons are capable of navigating through their usual terrain without guidance from motor axons. However, unlike motor axons, sensory axons do not appear to actively seek out appropriate target muscles when confronted with a novel terrain. These findings suggest that sensory neuron identity with regard to pathway and target choice may be unspecified or quite plastic at the time of initial axon outgrowth.     

Learning-induced improvement in encoding and decoding of specific movement directions by neurons in the primary motor cortex

Many recent studies describe learning-related changes in sensory and motor areas, but few have directly probed for improvement in neuronal coding after learning. We used information theory to analyze single-cell activity from the primary motor cortex of monkeys, before and after learning a local rotational visuomotor task. We show that after learning, neurons in the primary motor cortex conveyed more information about the direction of movement and did so with relation to their directional sensitivity. Similar to recent findings in sensory systems, this specific improvement in encoding is correlated with an increase in the slope of the neurons' tuning curve. We further demonstrate that the improved information after learning enables a more accurate reconstruction of movement direction from neuronal populations. Our results suggest that similar mechanisms govern learning in sensory and motor areas and provide further evidence for a tight relationship between the locality of learning and the properties of neurons; namely, cells only show plasticity if their preferred direction is near the training one. The results also suggest that simple learning tasks can enhance the performance of brain–machine interfaces.     

Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb

The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1) in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG), we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.