Brachially innervated ectopic hindlimbs in the chick embryo. II. The role of supraspinal input in the loss of limb motility

Brachially innervated grafted hindlimbs display a progressive loss of motility as development proceeds. However, the virtually immobile grafted hindlimbs of E20 embryos exhibited strong, synchronous contractions of gastrocnemius and tibialis muscles upon intraperitoneal injection of strychnine nitrate (20 μg). This result indicated that the marked behavioral deficit was not due to an inability of the motoneurons that innervate the immobile grafted hindlimbs to initiate and propagate action potentials, but was probably the result of an effective loss of motoneuron excitation. To examine the hypothesis that interaction with the supraspinal nervous system is involved in the reduction of grafted hindlimb activity, the normal forelimb and grafted hindlimb movements of chronic spinal embryos were examined. The normal forelimbs of chronic spinal embryos exhibited the same number of movements as normal embryos at all stages examined. Thus the deficit in grafted hindlimb motility is not comparable to the behavior of the normal forelimb in chronic spinal embryos and is, therefore, unlikely to be due to a lack of excitation from the supraspinal nervous system. The possibility of an inhibitory influence via supraspinal projections was examined in chronic spinal embryos that had brachially innervated grafted hindlimbs. After E12, the grafted hindlimbs of chronic spinal embryos displayed significantly fewer movements than the normal forelimbs of chronic spinal embryos but significantly more movements than the brachial hindlimb of embryos with intact spinal cords. By E18, however, both spinal and nonspinal brachial hindlimbs were equally dysfunctional. Thus prevention of supraspinal communication transiently reduces but does not prevent the emergence of motor dysfunction in the brachially innervated hindlimbs, which appears to be due to motoneurons not receiving sufficient net excitation, from spinal circuits, to propagate action potentials to the muscles. © 1993 John Wiley & Sons, Inc.     

Development and survival of thoracic motoneurons and hindlimb musculature following transplantation of the thoracic neural tube to the lumbar region in the chick embryo: functional aspects

Following heterotopic transplantation of the thoracic neural tube to the lumbar region on embryonic day (E) 2, the transplanted cord differentiates normally and establishes neuroanatomical connections with the host central nervous system and hindlimb muscles. Beginning on about E12, however, the neuromuscular system begins to undergo regressive changes resulting in motoneuron degeneration and muscle atrophy (O'Brien and Oppenheim, 1990). In the present paper, we have examined the development of neuromuscular function in thoracic transplant embryos from E6 to the time of hatching on E20-21. The onset of hindlimb movements and reflexes occurred at the same time (E6-E8) in both control and thoracic transplant embryos. Further, both the nature (pattern) and frequency of these movements appeared normal in the thoracic transplants up to E10-E12, after which there was a gradual and marked reduction in the frequency, and an alteration in the pattern, of both spontaneous and reflex-evoked hindlimb movements. After E16 normal movements were virtually absent in many of the thoracic transplant cases. By contrast, movements of the head, trunk and wings were normal in these embryos throughout the observation period. Hindlimbs innervated partly by the thoracic transplant and partly by remaining host lumbar cord did not exhibit the regressive changes in function after E10 that occurred in hindlimbs innervated exclusively by the thoracic transplant. EMG recordings from specific hindlimb muscles innervated solely by thoracic motoneurons demonstrated that the activation pattern of both flexors and extensors was similar to the repetitive pattern observed in normal thoracically innervated intercostal muscles (i.e., extensor-like). Muscles did not show distinguishable EMG burst patterns with inhibitory periods as do control lumbar innervated muscles. We conclude that the development of the pattern generating circuitry in the transplanted thoracic cord was similar to normal thoracic cord and thus appeared to be uninfluenced by having contacted the foreign hindlimb muscle targets early in development. Activity blockade with curare from E6 to E14 suppressed the loss of motoneurons that occurs in the thoracic transplant after E10. Thus, the abnormal thoracic-like activation pattern of thoracically innervated hindlimbs may be a critical signal in the initiation of the neuromuscular regression that occurs after E10 in these preparations. Finally, although the innervation and formation of neuromuscular endplates in thoracic transplants appeared normal up to E12, by E14 both the intramuscular nerves and the endplates exhibited signs of degeneration and regression. Thoracic motoneurons are initially able to innervate and functionally activate hindlimb muscles in a manner similar to that of thoracically innervated intercostal muscles.(ABSTRACT TRUNCATED AT 400 WORDS)     

Development and survival of thoracic motoneurons and hindlimb musculature following transplantation of the thoracic neural tube to the lumbar region in the chick embryo: anatomical aspects

Thoracic spinal cord transplanted to the lumbar region at the time of neural tube closure in the chick embryo survives and initially differentiates normally similar to in situ thoracic cord. Normal numbers of motoneurons are produced that innervate the host hindlimb musculature. In control thoracic cord approximately 70% of the motoneurons are lost by normal cell death between embryonic day (E) 6 and E11-E12. By contrast, the transplanted thoracic cord loses only about 30% of the motoneurons during this period. Transplantation of one hindlimb to the thoracic region also reduces the normal loss of in situ thoracic motoneurons. We conclude that some factor(s) associated with the increased target size provided by the hindlimbs promotes the survival of thoracic motoneurons. In contrast, by E16-E18 motoneuron numbers in the thoracic transplants decrease to below control levels. Dorsal root ganglion cells in the transplant were also initially increased (on E8) but later decreased to below control values. Hindlimb muscles innervated by thoracic motoneurons in the transplant also differentiated normally up to E10 to E12. Myotube size and numbers, muscle size and myotube types (fast versus slow) all developed normally in several thoracically-innervated hindlimb muscles. However, beginning on E14 myotube numbers and muscle size were markedly decreased resulting in muscle atrophy. Injections of horseradish peroxidase (HRP) into the thoracic transplants labelled neurons in the host spinal cord and brainstem rostral to the transplant thereby indicating an anatomical continuity between host and transplant neural tube. Injections of HRP into specific thoracically innervated hindlimb muscles on E8 labelled distinct pools of motoneurons in the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modifications of motoneuron development following transplantation of thoracic spinal cord to the lumbar region in the chick embryo: evidence for target-derived signals that regulate differentiation.

In order to examine the role of target cells in the development of spinal motoneurons, the neural tube from thoracic segments was transplanted to the lumbar region on embryonic day (E) 2, and allowed to innervate hindlimb muscles in the chick embryo. When examined at later stages of development, the proportion of white and gray matter in the thoracic transplant was altered to resemble normal lumbar cord. Many thoracic motoneurons were able to survive up to posthatching stages following transplantation. The branching and arborization of dendrites of thoracic motoneurons innervating hindlimb muscles, as well as motoneuron (soma) size, were also increased to an extent approximating that seen in normal lumbar motoneurons. In support of previous studies using a similar transplant model, we have also found that the peripheral (intramuscular) branching pattern of thoracic motoneuron axons innervating hindlimb muscles was similar to that of normal lumbar motoneurons. Axon size and the degree of myelination of transplanted thoracic motoneuron axons were also increased so that these parameters more closely resembled axons of normal lumbar than normal thoracic spinal motoneurons. Virtually all of the changes in motoneuron properties noted above were observed irrespective of whether or not the transplanted spinal cord had developed in anatomical continuity with the host rostral cord. Accordingly, it is unlikely that the changes in the development of transplanted thoracic motoneurons reported here are induced either entirely, or in part, by signals derived from the host central nervous system. Rather, these changes appear to be mediated by interactions between the transplanted motoneurons and the hindlimb. We favor the notion that retrograde trophic signals derived from the hindlimb act to modulate the development of innervating motoneurons. Whether this signal involves a diffusible trophic agent released from target cells, or acts by some other mechanism is presently unknown.     

Retinaldehyde dehydrogenase 2 and Hoxc8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons and the correct distribution of Islet1+ motoneurons

Retinoic acid (RA) activity plays sequential roles during the development of the ventral spinal cord. Here, we have investigated the functions of local RA synthesis in the process of motoneuron specification and early differentiation using a conditional knockout strategy that ablates the function of the retinaldehyde dehydrogenase 2 (Raldh2) synthesizing enzyme essentially in brachial motoneurons, and later in mesenchymal cells at the base of the forelimb. Mutant (Raldh2L-/-) embryos display an early embryonic loss of a subset of Lim1+ brachial motoneurons, a mispositioning of Islet1+ neurons and inappropriate axonal projections of one of the nerves innervating extensor limb muscles, which lead to an adult forepaw neuromuscular defect. The molecular basis of the Raldh2L-/- phenotype relies in part on the deregulation of Hoxc8, which in turn regulates the RA receptor RARbeta. We further show that Hoxc8 mutant mice, which exhibit a similar congenital forepaw defect, display at embryonic stages molecular defects that phenocopy the Raldh2L-/- motoneuron abnormalities. Thus, interdependent RA signaling and Hox gene functions are required for the specification of brachial motoneurons in the mouse.     

Modifications of motoneuron development following transplantation of thoracic spinal cord to the lumbar region in the chick embryo: Evidence for target-derived signals that regulate differentiation

In order to examine the role of target cells in the development of spinal motoneurons, the neural tube from thoracic segments was transplanted to the lumbar region on embryonic day (E) 2, and allowed to innervate hindlimb muscles in the chick embryo. When examined at later stages of development, the proportion of white and gray matter in the thoracic transplant was altered to resemble normal lumbar cord. Many thoracic motoneurons were able to survive up to posthatching stages following transplantation. The branching and arborization of dendrites of thoracic motoneurons innervating hindlimb muscles, as well as motoneuron (soma) size, were also increased to an extent approximating that seen in normal lumbar motoneurons. In support of previous studies using a similar transplant model, we have also found that the peripheral (intramuscular) branching pattern of thoracic motoneuron axons innervating hindlimb muscles was similar to that of normal lumbar motoneurons. Axon size and the degree of myelination of transplanted thoracic motoneuron axons were also increased so that these parameters more closely resembled axons of normal lumbar than normal thoracic spinal motoneurons. Virtually all of the changes in motoneuron properties noted above were observed irrespective of whether or not the transplanted spinal cord had developed in anatomical continuity with the host rostral cord. Accordingly, it is unlikely that the changes in the development of transplanted thoracic motoneurons reported here are induced either entirely, or in part, by signals derived from the host central nervous system. Rather, these changes appear to be mediated by interactions between the transplanted motoneurons and the hindlimb. We favor the notion that retrograde trophic signals derived from the hindlimb act to modulate the development of innervating motoneurons. Whether this signal involves a diffusible trophic agent released from target cells, or acts by some other mechanism is presently unknown. © 1992 John Wiley & Sons, Inc.     

Evidence that regenerative ability is an intrinsic property of limb cells in Xenopus

Xenopus laevis exhibits an ontogenetic decline in the ability to regenerate its limbs: Young tadpoles can completely regenerate an amputated limb, whereas post metamorphic froglets regenerate at most a cartilagenous "spike." We have tested the regenerative competence of normally regenerating limb buds of stage 52-53 Xenopus tadpoles grafted onto limb stumps of postmetamorphic froglets. The limb buds become vascularized and innervated by the host and, when amputated, regenerate limbs with normal or slightly less than normal numbers of tadpole hindlimb digits. Reciprocal grafts of froglet forelimb blastemas onto tadpole hindlimb stumps resulted in either autonomous development of tadpole hindlimb structures and/or formation of a cartilaginous spike typical of froglet forelimb regeneration. Our results suggest that the Xenopus froglet host environment is completely permissive for regeneration and that the ability to regenerate a complete limb pattern is an intrinsic property of young tadpole limb cells, a property that is lost during ontogenesis.     

Myogenic defect in muscular dystrophy of the chicken.

Inherited muscular dystrophy of the chicken is thought to arise from abnormal development of trophic regulation of skeletal muscles by their innervating nerves. To determine whether expression of muscular dystrophy in the chicken is a property of the nerves or of the muscles, wing limb buds were transplanted between normal and dystrophic chick embryos at $\text{3}\text{1}\text{2}$ days of incubation (stage 19–20). Muscles of donor limbs innervated by nerves of the hosts were compared to contralateral unoperated host limb muscles in chicks from 6 to 25 weeks after hatching. Expression of normal or dystrophic phenotype was determined by examination of five different properties which are altered in dystrophic chick muscle: electromyographic evidence of myotonia; fiber diameter; acetylcholinesterase activity, localization, and isozymes; lactic dehydrogenase activity; and succinic dehydrogenase activity. Genetically normal muscle innervated by nerves of normal or dystrophic hosts was phenotypically normal while genetically dystrophic muscle innervated by normal nerves was phenotypically dystrophic. The results suggest that inherited muscular dystrophy of the chicken arises from a defect of muscle rather than from a lesion in the nerves themselves.     

Motoneuron projection patterns in chick embryonic limbs with a double complement of dorsal thigh musculature

During the normal development of the chick, lateral motoneurons within the lumbosacral motor column of the spinal cord consistently project to muscles of dorsal origin within the limb while medial motoneurons project to muscles of ventral origin. To determine if specific cues arising from each type of target are the dominant guidance cues used by lateral and medial motoneurons to create this pattern, I examined motoneuron projections in embryonic chick limbs with a double complement of dorsal thigh musculature and no ventral musculature. Results indicate that cues associated with muscles of a specific developmental origin do not invariably dominate. Before and after the major period of motoneuron death, all muscles in dorsal limb regions (host) were innervated by lateral or dorsal pool neurons. Most ventrally positioned (donor) muscles were innervated by medial or ventral pool neurons. Only the donor iliofibularis, a muscle located very near to its original source of innervation, received projections from some lateral neurons. Within the limb proper, medial or ventral pool neurons projected to donor muscles in a patterned manner suggesting that they were following nonspecific regional cues and perhaps also responding to the availability of uninnervated target tissue. I conclude that axon sorting into distinct lateral and medial classes is independent of limb target complement and that subsequent pathway choice is a separate event governed by both specific target cues and other guidance mechanisms.     

视黄酸挽救的视黄酸合成酶Raldh2基因敲除鼠E10.75胚胎后肢发育正常

视黄酸合成酶Raldh2基因敲除鼠胚胎没有肢体的发育在胚胎E6.75-E 8.25期间,喂给怀孕母鼠含视黄酸（0.1 mg/g食物）食物后,Raldh2基因敲除鼠E10.75胚胎后肢形态正常,前肢发育较小.原位杂交结果表明,决定肢体近 远端轴发育的标志基因(marker gene)Fgf8,决定前-后轴发育的标志基因Shh以及后肢发育特异性基因Tbx4 和Pitx1在视黄酸挽救的Raldh2基因敲除鼠E10.75胚胎的后肢表达正常.上述结果提示,视黄酸可以挽救Raldh2基因敲除鼠E10.75胚胎后肢的正常发育.     

Effects of hindlimb suspension on soleus muscle fibers and their spinal motoneurons in Wistar Hannover rats

Cross-sectional areas and succinate dehydrogenase (SDH) activities of soleus muscle fibers and their spinal motoneurons in male Wistar Hannover rats were determined after 16 days of hindlimb suspension. A decreased percentage of type I fibers and an increased percentage of type I+II fibers were observed after hindlimb suspension. Cross-sectional areas of all types of fibers were smaller in the hindlimb suspended than control rats. SDH activities of all types of fibers did not change after hindlimb suspension. Numbers, cross-sectional areas, or SDH activities of spinal motoneurons did not change after hindlimb suspension. It is suggested that spinal motoneurons innervating the rat soleus muscle are not affected by decreased neuromuscular activity on Earth and that gravity itself is important for maintaining of spinal motoneuron metabolic properties.     

Evidence that some developing limb motoneurons die for reasons other than peripheral competition

In vertebrate embryos up to 75% of lateral motor column (LMC) cells die soon after innervating the limb bud. The hypothesis was tested that competition for unknown limb factors may decide which cells will survive. Removal of the future knee flexor motoneurons before the onset of cell death was attempted with varying success in Xenopus laevis tadpoles by removing a piece of spinal cord containing the rostral part of the left lumbar LMC. In normal tadpoles, hundreds of cells in the caudal part of the LMC temporarily project to the presumptive knee flexors and are among the first to die. The competition hypothesis predicts that they should remain alive after a successful operation. After maturation the most successful operations were found to have resulted in paralysis and hypoplasia of the knee flexors. Horseradish peroxidase tracing techniques confirmed that the knee flexors were not innervated. However, ankle and foot movements were normal indicating that the remaining caudal LMC cells had developed their normal projections to the distal limb. The failure to survive of the caudal LMC cells projecting to the knee flexors, despite the absence of rostral LMC cell innervation, shows that factors other than competition must control at least some LMC cell deaths.     

The effect of somite manipulation on the development of motoneuron projection patterns in the embryonic chick hindlimb

Although the formation of motoneuron projections to individual muscles in the embryonic chick hindlimb has been shown to involve the specific recognition of environmental cues, the source of these cues and their mode of acquisition are not known. I show in the accompanying paper (C. Lance-Jones, 1988, Dev. Biol. 126, 394-407) that there is a correlation between the segmental level of origin of motoneurons and the somitic level of origin of the muscle cells of their targets in the chick hindlimb. These data are compatible with the hypothesis that the developmental basis for specific recognition is a positional one. Motoneurons and myogenic cells may be uniquely labeled in accord with their axial level of origin early in development and subsequently matched on the basis of these labels. To test this hypothesis, I have assessed motoneuron projection patterns in the embryonic chick hindlimb after somitic tissue manipulations. In one series of embryos, somitic mesoderm at levels 26-29 or 27-29 was reversed about the anteroposterior axis prior to myogenic cell migration and axon outgrowth. Since previous studies have shown that cells migrate from the somites in accord with their position and that somites 26-29 populate anterior thigh musculature, this operation will have reversed the somitic level of origin of anterior thigh muscles. Retrograde HRP labeling of projections to anterior thigh muscles at stage (st) 30 and st 35-38 showed that motoneuron projections were largely normal. This finding suggests that limb muscle cells or their source, the somites, do not contain the cues responsible for specific recognition prior to myogenic cell migration and axon outgrowth. To confirm that specific guidance cues were still intact after somitic mesoderm reversal, I also assessed motoneuron projections in embryos where somitic tissue plus adjacent spinal cord segments at levels 26-29 were reversed in a similar manner. Analyses of the distribution of retrogradely labeled motoneurons in reversed cord segments at st 35-36 indicated that motoneuron projections were reversed. This finding suggests that motoneurons have altered their course to project to correct targets despite the altered somitic origin of their targets and, thus, that specific guidance cues were intact. I conclude that if cues governing target or pathway choice are encoded positionally then they must be associated with other embryonic tissues such as the connective tissues or that guidance cues are acquired by myogenic cells after the onset of migration and motoneuron specification.     

Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function

The secreted protein encoded by the Sonic hedgehog (Shh) gene is localized to the posterior margin of vertebrate limb buds and is thought to be a key signal in establishing anterior-posterior limb polarity. In the Shh(-/-) mutant mouse, the development of many embryonic structures, including the limb, is severely compromised. In this study, we report the analysis of Shh(-/-) mutant limbs in detail. Each mutant embryo has four limbs with recognizable humerus/femur bones that have anterior-posterior polarity. Distal to the elbow/knee joints, skeletal elements representing the zeugopod form but lack identifiable anterior-posterior polarity. Therefore, Shh specifically becomes necessary for normal limb development at or just distal to the stylopod/zeugopod junction (elbow/knee joints) during mouse limb development. The forelimb autopod is represented by a single distal cartilage element, while the hindlimb autopod is invariably composed of a single digit with well-formed interphalangeal joints and a dorsal nail bed at the terminal phalanx. Analysis of GDF5 and Hoxd11-13 expression in the hindlimb autopod suggests that the forming digit has a digit-one identity. This finding is corroborated by the formation of only two phalangeal elements which are unique to digit one on the foot. The apical ectodermal ridge (AER) is induced in the Shh(-/-) mutant buds with relatively normal morphology. We report that the architecture of the Shh(-/-) AER is gradually disrupted over developmental time in parallel with a reduction of Fgf8 expression in the ridge. Concomitantly, abnormal cell death in the Shh(-/-) limb bud occurs in the anterior mesenchyme of both fore- and hindlimb. It is notable that the AER changes and mesodermal cell death occur earlier in the Shh(-/-) forelimb than the hindlimb bud. This provides an explanation for the hindlimb-specific competence to form autopodial structures in the mutant. Finally, unlike the wild-type mouse limb bud, the Shh(-/-) mutant posterior limb bud mesoderm does not cause digit duplications when grafted to the anterior border of chick limb buds, and therefore lacks polarizing activity. We propose that a prepattern exists in the limb field for the three axes of the emerging limb bud as well as specific limb skeletal elements. According to this model, the limb bud signaling centers, including the zone of polarizing activity (ZPA) acting through Shh, are required to elaborate upon the axial information provided by the native limb field prepattern.     

Cell death of motoneurons in the chick embryo spinal cord. XI. Acetylcholine receptors and synaptogenesis in skeletal muscle following the reduction of motoneuron death by neuromuscular blockade

Treatment of chick embryos with neuromuscular blocking agents such as curare during periods of naturally occurring motoneuron death results in a striking reduction of this normal cell loss. Inactivity-induced changes in motoneuron survival were found to be associated with increased levels of AChRs and AChR-clusters in skeletal muscle and with increased focal sites of AChE that are innervated ('synaptic sites'). Treatment of embryos with curare after the normal cell death period (E12-E15) resulted in no change in motoneuron survival. Although AChR-clusters and focal sites of AChE were increased in these embryos on E16, many of these sites were uninnervated. Treatment of embryos with nicotine or decamethonium (E6-E10) also reduced neuromuscular activity but did not alter motoneuron survival nor did such treatment alter AChRs. The different effects of curare vs nicotine and decamethoniam on motoneuron survival and AChRs may be related to the fact that the former is a competitive blocker whereas the latter two drugs are depolarizing blockers. Finally, treatment of embryos (E6-9) with doses of curare (1 mg daily) that allow for the almost complete recovery of neuromuscular activity a few days following treatment (by E16) resulted in the gradual loss of the excess motoneurons that were present on E10, and by E16 the number of remaining AChR clusters and focal sites of AChE were also decreased to levels comparable to control values. Inactivity-induced changes in AChRs or AChR-clusters may be an important factor in the reduced motoneuron death that accompanies neuromuscular blockade during critical stages of development. These receptor changes very likely reflect increased synaptogenesis in the muscles of paralyzed embryos which in turn may act to reduce motoneuron death by providing increased access to muscle-derived neurotrophic molecules.     

Quadrupedal locomotion in squirrel monkeys (Cebidae: Saimiri sciureus): a cineradiographic study of limb kinematics and related substrate reaction forces

Quadrupedal locomotion of squirrel monkeys on small-diameter support was analyzed kinematically and kinetically to specify the timing between limb movements and substrate reaction forces. Limb kinematics was studied cineradiographically, and substrate reaction forces were synchronously recorded. Squirrel monkeys resemble most other quadrupedal primates in that they utilize a diagonal sequence/diagonal couplets gait when walking on small branches. This gait pattern and the ratio between limb length and trunk length influence limb kinematics. Proximal pivots of forelimbs and hindlimbs are on the same horizontal plane, thus giving both limbs the same functional length. However, the hindlimbs are anatomically longer than the forelimbs. Therefore, hindlimb joints must be more strongly flexed during the step cycle compared to the forelimb joints. Because the timing of ipsilateral limb movements prevents an increasing amount of forelimb retraction, the forelimb must be more protracted during the initial stance phase. At this posture, gravity acts with long moment arms at proximal forelimb joints. Squirrel monkeys support most of their weight on their hindlimbs. The timing of limb movements and substrate reaction forces shows that the shift of support to the hindlimbs is mainly done to reduce the compressive load on the forelimb. The hypothesis of the posterior weight shift as a dynamic strategy to reduce load on forelimbs, proposed by Reynolds ([1985]) Am. J. Phys. Anthropol. 67:335-349; [1985] Am. J. Phys. Anthropol. 67:351-362), is supported by the high correlation of ratios between forelimb and hindlimb peak vertical forces and the range of motion of shoulder joint and scapula in primates.     

Peripheral specification of Ia synaptic input to motoneurons innervating foreign target muscles

Muscle sensory neurons, called Ia afferents, make monosynaptic connections with functionally related sets of motoneurons in the spinal cord. Previous work has suggested that peripheral target muscles play a major role in determining the central connections of Ia afferents with motoneurons. Here, we ask whether motoneurons can also be influenced by their target muscles in terms of the monosynaptic input they receive from Ia afferents, by transplanting thoracic motoneurons into the lumbosacral spinal cord so that they innervate foreign muscles. Three or four segments of thoracic neural tube from stage 14-15 chicken embryos were transplanted to the lumbosacral region of stage 16-17 embryos, and electrophysiological recordings were made from transplanted motoneurons after the embryos had reached stage 38-40. Transplanted thoracic motoneurons innervated limb muscles and received monosynaptic inputs from Ia afferents. These connections were not random: Most of the connections were formed between Ia afferents and motoneurons projecting to the same muscle (homonymous connections). Few aberrant connections were found although the anatomical distribution of afferents in the transplant indicated that they had ample opportunity to contact inappropriate motoneurons. We conclude that although peripheral target cues are not sufficient to respecify an already committed motoneuron (turn a thoracic motoneuron into a lumbosacral motoneuron), they do provide sufficient information for Ia afferent input to be functionally correct.     

The effects of long-standing limb loss on anatomical reorganization of the somatosensory afferents in the brainstem and spinal cord

We examined the terminations of sensory afferents in the brainstem and spinal cord of squirrel monkeys and prosimian galagos 4-8 years after a therapeutic forelimb or hindlimb amputation within 2 months of birth. In each animal, the distributions of labeled sensory afferent terminations from remaining body parts proximal to the limb stump were much more extensive than in normal animals. These sprouted afferents extended into the portions of the dorsal horn of the spinal cord as well as the cuneate and external cuneate nuclei of the brainstem (forelimb amputees) or spinal Clarke's column (hindlimb amputee) related to the amputated limb. Such reorganization in sensory afferents along with reorganization of the motor efferents to muscles (Wu and Kaas, J Neurosci 19 : 7679-7697, 1999, Neuron 28 : 967-978, 2000) may provide a basis for mislocated phantom sensations of missing forelimb movements accompanying actual shoulder movements during cortical stimulation or movement imagery in patients with amputations.     

The effects of long-standing limb loss on anatomical reorganization of the somatosensory afferents in the brainstem and spinal cord

We examined the terminations of sensory afferents in the brainstem and spinal cord of squirrel monkeys and prosimian galagos 4-8 years after a therapeutic forelimb or hindlimb amputation within 2 months of birth. In each animal, the distributions of labeled sensory afferent terminations from remaining body parts proximal to the limb stump were much more extensive than in normal animals. These sprouted afferents extended into the portions of the dorsal horn of the spinal cord as well as the cuneate and external cuneate nuclei of the brainstem (forelimb amputees) or spinal Clarke's column (hindlimb amputee) related to the amputated limb. Such reorganization in sensory afferents along with reorganization of the motor efferents to muscles (Wu and Kaas, J Neurosci 19: 7679-7697, 1999, Neuron 28: 967-978, 2000) may provide a basis for mislocated phantom sensations of missing forelimb movements accompanying actual shoulder movements during cortical stimulation or movement imagery in patients with amputations.