Ethanol influences on the chick embryo spinal cord motor system: Analyses of motoneuron cell death,motility, and target trophic factor activity and in vitro analyses of neurotoxicity and trophic factor neuroprotection

A series of in vivo and in vitro experiments were conducted to determine the influence of prenatally administered ethanol on several aspects of the developing chick embryo spinal cord motor system. Specifically, we examined: (1) the effect of chronic ethanol administration during the natural cell death period on spinal cord motoneuron numbers; (2) the influence of ethanol on ongoing embryonic motility; (3) the effect of ethanol exposure on neurotrophic activity in motoneuron target tissue (limbbud); and (4) the responsiveness of cultured spinal cord neurons to ethanol, and the potential of target-derived neurotrophic factors to ameliorate ethanol neurotoxicity. These studies revealed the following: Chronic prenatal ethanol exposure reduces the number of motoneurons present in the lateral motor column after the cell death period [embryonic day 12 (E12)]. Ethanol tends to inhibit embryonic motility, particularly during the later stages viewed (E9-E11). Chronic ethanol exposure reduces the neurotrophic activity contained in target muscle tissue. Such diminished support could contribute to the observed motoneuron loss. Direct exposure of spinal cord neurons to ethanol decreases neuronal survival and process outgrowth in a dose-dependent manner, but the addition of target muscle extract to ethanol-containing cultures can ameliorate this ethanol neurotoxicity. These studies demonstrate ethanol toxicity in a population not previously viewed in this regard and suggest a mechanism that may be related to this cell loss (i.e., decreased neurotrophic support). © 1995 John Wiley & Sons, Inc.     

Interactions between spinal cord stimulation and activity blockade in the regulation of synaptogenesis and motoneuron survival in the chick embryo

The present study investigated the effects of spinal cord stimulation, neuromuscular blockade, or a combination of the two on neuromuscular development both during and after the period of naturally occurring motoneuron death in the chick embryo. Electrical stimulation of the spinal cord was without effect on motoneuron survival, synaptogenesis, or muscle properties. By contrast, activity blockade rescued motoneurons from cell death and altered synaptogenesis. A combination of spinal cord stimulation and activity blockade resulted in a marked increase in motoneuron death, and also altered synaptogenesis similar to that seen with activity blockade alone. Perturbation of normal nerve–muscle interactions by activity blockade may increase the vulnerability of developing motoneurons to excessive excitatory afferent input (spinal cord stimulation) resulting in excitotoxic-induced cell death. © 1993 John Wiley & Sons, Inc.     

Effects of testosterone on the development of a sexually dimorphic neuromuscular system in ciliary neurotrophic factor receptor knockout mice

Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) innervate the perineal muscles, bulbocavernosus (BC), and levator ani (LA). Testosterone regulates the survival of SNB motoneurons and BC/LA muscles during perinatal life. Previous findings suggest that effects of testosterone on this system may be mediated by trophic factors—in particular, by a factor acting through the ciliary neurotrophic factor α‐receptor (CNTFRα). To test the role of CNTFRα in the response of the developing SNB system to testosterone, CNTFRα +/+ and −/− mice were treated with testosterone propionate (TP) or oil during late embryonic development. BC/LA muscle size and SNB motoneuron number were evaluated on the day of birth. Large sex differences in BC and LA muscle size were present in newborn mice of both genotypes, but muscle volumes were reduced in CNTFRα −/− animals relative to same‐sex, wild‐type controls. Prenatal testosterone treatment completely eliminated the sex difference in BC/LA muscle size in wild‐type animals, and eliminated the effect of the CNTFRα gene deletion on muscle size in males. However, the effect of TP treatment on BC and LA muscle sizes was blunted in CNTFRα −/− females. SNB motoneuron number was sexually dimorphic in oil‐treated, wild‐type mice. In contrast, there was no sex difference in SNB motoneuron number in oil‐treated, CNTFRα knockout mice. Prenatal treatment with testosterone did not increase SNB motoneuron number in CNTFRα −/− mice, but also did not significantly increase SNB motoneuron number in newborn wild‐type animals. These findings confirm the absence of a sex difference in SNB motoneuron number in CNTFRα −/− mice. Moreover, the CNTFRα gene deletion influences perineal muscle development and the response of the perineal muscles to testosterone. Prenatal TP treatment of CNTFRα −/− males overcomes the effects of the gene deletion on the BC and LA muscles without a concomitant effect on SNB motoneuron number. © 1999 John Wiley & Sons, Inc. J Neurobiol 41: 317–325, 1999     

Brachially innervated ectopic hindlimbs in the chick embryo. I. Limb motility and motor system anatomy during the development of embryonic behavior

The functional status of brachially innervated hindlimbs, produced by transplanting hindlimb buds of chick embryos in place of forelimb buds, was quantified by analyzing the number and temporal distribution of spontaneous limb movements. Brachially innervated hindlimbs exhibited normal motility until E10 but thereafter became significantly less active than normal limbs and the limb movements were more randomly distributed. Contrary to the findings with axolotls and frogs, functional interaction between brachial motoneurons and hindlimb muscles cannot be sustained in the chick embryo. Dysfunction is first detectable at E10 and progresses to near total immobility by E20 and is associated with joint ankylosis and muscular atrophy. Although brachially innervated hindlimbs were virtually immobile by the time of hatching (E21), they produced strong movements in response to electrical stimulation of their spinal nerves, suggesting a central rather than peripheral defect in the motor system. The extent of motoneuron death in the brachial spinal cord was not significantly altered by the substitution of the forelimb bud with the hindlimb bud, but the timing of motoneuron loss was appropriate for the lumbar rather than brachial spinal cord, indicating that the rate of motoneuron death was dictated by the limb. Measurements of nuclear area indicated that motoneuron size was normal during the motoneuron death period (E6-E10) but the nuclei of motoneurons innervating grafted hindlimbs subsequently became significantly larger than those of normal brachial motoneurons. Although the muscle mass of the grafted hindlimb at E18 was significantly less than that of the normal hindlimb (and similar to that of a normal forelimb), electronmicroscopic examination of the grafted hindlimbs and brachial spinal cords of E20 embryos revealed normal myofiber and neuromuscular junction ultrastructure and a small increase in the number of axosomatic synapses on cross-sections of motoneurons innervating grafted hindlimbs compared to motoneurons innervating normal forelimbs. The anatomical data indicate that, rather than being associated with degenerative changes, the motor system of the brachial hindlimb of late-stage embryos is intact, but inactive. © 1993 John Wiley & Sons, Inc.     

A cellular taxonomy of the adult human spinal cord

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A radiometric microassay for choline acetyltransferase. Some observations on the spinal cord of the chicken embryo

This paper describes cation-exchange methods for separating acetyl[³H] coenzyme A from [acetyl-³H]choline. Blanks for the routine method were approximately 0.05% of the substrate radioactivity; product recoveries were approximately 97%. The cation-exchange method was moreefficient than the standard methods using either anion-exchange chromatography or periodide precipitation. The cation-exchange method was also morespecific than either of the other two standard methods for estimating choline acetyltransferase (ChAT) activity. ChAT activity was detected in the chicken lumbar spinal cord on embryonic day (E) 2 1/4 with the cation-exchange method. This developmental stage is about 6 hours before the final mitosis of any neuroblast in the ventral horn. Total ChAT activity per lumbar spinal cord increased more than 10,000-fold between E 3 and E 18. Changes in ChAT activity in the lumbar spinal cord following limb-bud extirpation appeared to mirror (with a phase lag) the changes in the number of motoneurons in the lateral motor column.     

P2X7 purinoceptors contribute to the death of Schwann cells transplanted into the spinal cord

The potential to use Schwann cells (SCs) in neural repair for patients suffering from neurotrauma and neurodegenerative diseases is well recognized. However, significant cell death after transplantation hinders the clinical translation of SC-based therapies. Various factors may contribute to the death of transplanted cells. It is known that prolonged activation of P2X7 purinoceptors (P2X7R) can lead to death of certain types of cells. In this study, we show that rat SCs express P2X7R and exposure of cultured SCs to high concentrations of ATP (3–5 mM) or a P2X7R agonist, 2′(3′)-O-(4-benzoylbenzoyl)ATP (BzATP) induced significant cell death rapidly. High concentrations of ATP and BzATP increased ethidium uptake by SCs, indicating increased membrane permeability to large molecules, a typical feature of prolonged P2X7R activation. SC death, as well as ethidium uptake, induced by ATP was blocked by an irreversible P2X7R antagonist oxidized ATP (oxATP) or a reversible P2X7R antagonist A438079. oxATP also significantly inhibits the increase of intracellular free calcium induced by minimolar ATP concentrations. Furthermore, ATP did not cause death of SCs isolated from P2X7R-knockout mice. All these results suggest that P2X7R is responsible for ATP-induced SC death in vitro. When rat SCs were treated with oxATP before transplantation into uninjured rat spinal cord, 35% more SCs survived than untreated SCs 1 week after transplantation. Moreover, 58% more SCs isolated from P2X7R-knockout mice survived after being transplanted into rat spinal cord than SCs from wild-type mice. This further confirms that P2X7R is involved in the death of transplanted SCs. These results indicate that targeting P2X7R on SCs could be a potential strategy to improve the survival of transplanted cells. As many other types of cells, including neural stem cells, also express P2X7R, deactivating P2X7R may improve the survival of other types of transplanted cells.     

伸长细胞移植对大鼠脊髓损伤后运动功能及运动诱发电位的影响

目的:研究伸长细胞是否可以促进成年大鼠脊髓损伤后传导束再生。方法:采用Wistar大鼠脊髓T8全横断模型,移植传代培养的伸长细胞,以未移植脊髓损伤组为对照,观察两组损伤后第12周末BBB评分,损伤平面以下红核-脊髓运动诱发电位,和横断部位组织学染色结果。结果:第12周末伸长细胞移植组红核脊髓运动诱发电位总峰值显著高于对照组(MD=133.2μV,P0.01),峰潜伏期较对照组缩短(MD=0.061ms,P=0.040);第12周末伸长细胞移植组BBB评分显著高于对照组(MD=5.0000,P0.01);第12周末脊髓横断部位HE染色显示伸长细胞移植组脊髓损伤处结构较完整。结论:伸长细胞移植可以促进大鼠脊髓损伤后神经传导的恢复。     

Nicotine protects against arachidonic-acid-induced caspase activation, cytochrome c release and apoptosis of cultured spinal cord neurons

Hydrolysis of membrane phospholipids of spinal cord neurons is one of the first events initiated in spinal cord trauma. In this process, free fatty acids, and in particular arachidonic acid, are released. Exposure of spinal cord neurons to free arachidonic acid can compromise cell survival and initiate apoptotic cell death. In order to determine potential mechanisms of apoptosis induced by arachidonic acid, activation of caspases -3, -8, and -9, as well as the release of cytochrome c into the cytoplasm were measured in cultured spinal cord neurons exposed to 10 microM of this fatty acid. In addition, because nicotine can exert a variety of neuroprotective effects, we hypothesized that it can prevent arachidonic acid induced apoptosis of spinal cord neurons. To study this hypothesis, spinal cord neurons were pretreated with nicotine (10 microM for 2 h) before arachidonic acid exposure and caspase activation as well as markers of apoptotic cell death were studied. Treatment of spinal cord neurons with arachidonic acid for up to 24 h significantly increased cytoplasmic levels of cytochrome c, induced caspase activation and induced DNA laddering, a hallmark of apoptotic cell death. Nicotine pretreatment markedly attenuated all these effects. In addition, antagonist studies suggest that the alpha7 nicotinic receptor is primarily responsible for these anti-apoptotic effects of nicotine. These results indicate that nicotine can exert potent neuroprotective effects by inhibiting arachidonic acid induced apoptotic cascades of spinal cord neurons.     

米诺环素对不完全脊髓损伤大鼠脊髓BDNF和NT-3表达的影响

目的观察腹腔注射米诺环素对改良Allen’s法造成的不完全脊髓损伤大鼠脊髓中脑源性神经营养因子以及神经营养因子3表达的影响,探讨米诺环素治疗脊髓损伤的作用机制。方法成年雌性Sprague-Dawley(SD)大鼠54只,改良Allen’s法造成不完全脊髓损伤,根据实验需要可以分为3组,空白组,只打开脊柱椎板,不损伤;治疗组,大鼠脊髓损伤,并腹腔注射米诺环素;损伤组,大鼠脊髓损伤,腹腔注射等剂量的生理盐水。观察各组大鼠的后肢能力Basso-Beattie-Bresnahan评分,并于不同时段(3d、7d,14d)取大鼠脊髓T8-9段采用逆转录PCR,以及免疫化学组织染色法测定脑源性神经营养因子以及神经营养因子3的表达。结果米诺环素能够明显改善不完全脊髓损伤大鼠的功能,逆转录PCR和脊髓组织冰冻切片免疫组织化学染色DAB都能证实米诺环素治疗组脑源性神经营养因子以及神经营养因子3表达显著增多。结论米诺环素在治疗不完全脊髓损伤大鼠的机制还应与其上调了大鼠体内的脑源性神经营养因子以及神经营养因子3表达有关。     

Lack of evidence for cell death among avian spinal cord interneurons during normal development and following removal of targets and afferents

Chick embryos and posthatched chicks were examined at several ages for the presence of pyknotic interneurons in the lumbar spinal cord. Because no pyknotic interneurons were found, direct cell counts of healthy interneurons were carried out and a comparison made between early-and late-stage embryos and hatchlings. There was no decrease in the number of interneurons in the ventral intermediate gray matter of the spinal cord between embryonic day (E) 8 and 2 weeks posthatching (PH) or in the dorsal horn between E10 and 2 weeks PH. To study whether interneuron survival is regulated by targets or afferents, a situation known to exist in other developing neural populations, early embryos were subjected to (1) removal of one limb, resulting in the loss of lateral motor column motoneurons and dorsal root ganglion sensory afferents; (2) transection of the thoracic spinal cord, thereby removing both descending afferents and rostral targets of spinal interneurons, or (3) a combination of the two operations. No reductions in interneuron numbers were found as a result of these operations. Furthermore, morphometric analysis also revaled no change in neuronal size following these experimental manipulations. By contrast, there was a slight decrease in the total area of spinal gray matter that was most prominent in the dorsal region following limb bud removal. Our results indicate (1) that spinal interneurons fail to exhibit the massive naturally occurring death of postmitotic neurons that has been observed for several other populations of spinal neurons, and (2) spinal interneurons appear to be relatively resistant to induced cell death following the removal of substantial numbers of afferent inputs and targets.     

Cell death of motoneurons in the chick embryo spinal cord. X. Synapse formation on motoneurons following the reduction of cell death by neuromuscular blockade

Chronic treatment of chick embryos with neuromuscular blocking agents, such as curare, rescues motoneurons from naturally occurring cell death. In the present study, embryos treated with curare from E6 to E9 had 35% more motoneurons than controls on E10 and 42% more than controls on E16. Previous studies have shown that several aspects of motoneuron differentiation occur normally in curare-treated embryos. We report here that dendrite growth and arborization is also unaltered on E10 and E16 following curare treatment. A quantitative analysis of afferent synapses on motoneurons shows that the packing density of both axosomatic and axodendritic synapses is also normal on E10 in curare-treated embryos, despite the greater number of motoneurons present. This indicates that the interneurons that provide presynaptic input to motoneurons are able to compensate for the increased number of synaptic sites made available by curare treatment. However, by E16 the packing density of synapses is reduced by about half. Because motoneurons and their dendrites continue to grow between E10 and E16, the further increase in synaptic sites made available in curare-treated embryos apparently exceeds the compensatory capacity of presynaptic interneurons on E16. One can conclude from these results that the increased survival of motoneurons in curare-treated embryos is not owing to an increase in afferent synapses. Motoneurons in these embryos continue to survive in the face of either no change (E10) or a reduction (E16) in the number of axodendritic and axosomatic synapses. Therefore, increased motoneuron survival in this situation is very likely regulated primarily by motoneuron-target interactions.     

Effects of ethanol on rat schwann cell proliferation and myelination in culture

Summary It is possible to treat dissociated embryonic rat dorsal root ganglia in culture to inhibit proliferation of all nonneuronal cells except Schwann cells. Neurons have been shown to produce a mitogenic stimulus for Schwann cells under these conditions. Additionally, myelin-competent neurons induce Schwann cells to elaborate myelin sheaths. Groups of sibling cultures were exposed to various nonlethal concentrations of ethanol (0, 43, 86, or 172 mM) for 4 wk. Culture were assessed weekly by light microscopy in a blind fashion for evidence of Schwann cell proliferation and myelin formation. Ethanol adversely affected both Schwann cell proliferation and myelin formation in culture. No obvious differences in neuronal morphology were observed among the various groups of cultures by light or electron microscopy. These observations suggest that ethanol might interfere with Schwann cell proliferation and myelin formation in culture by one or both of the following means: a) inhibit neuronal production of signals for Schwann cell proliferation and myelination or b) impede Schwann cell responses to neuronal signals. Investigation of these possibilities in culture may provide insight into neuropathologic mechanisms operative in the fetal alcohol syndrome or alcohol-associated peripheral neuropathy in humans. This work was supported by the Department of Veterans Affairs, Washington, D.C.     

Expression and androgen regulation of the ciliary neurotrophic factor receptor (CNTFRα) in muscles and spinal cord

We have previously observed that ciliary neurotrophic factor (CNTF) can prevent the degeneration of androgen-sensitive perineal motoneurons and their target muscles, the bulbocavernosus and levator ani (BC/LA), in perinatal female rats. Response to CNTF is dependent on the expression of the alpha component of the CNTF receptor (CNTFRα). In the present study, we examined the developmental profile and androgen regulation of CNTFRα gene expression in BC/LA muscle, thigh muscle, and lumbosacral spinal cord. CNTFRα mRNA was abundantly expressed in the BC/LA and thigh around the time of birth; expression declined progressively after birth and remained low into adulthood. In contrast, CNTFRα message remained high in the lumbosacral spinal cord throughout development. Androgen regulation of CNTFRα expression was examined in prenatal animals by administering the androgen receptor blocker hydroxyflutamide from embryonic days E18 through E21. Four days of androgen deprivation caused a significant up-regulation of CNTFRα mRNA in the BC/LA, thigh, and spinal cord of male fetuses. After castration in adulthood, CNTFRα expression in the BC/LA transiently increased, then decreased below control levels. Expression of CNTFRα in thigh muscles and the lumbosacral spinal cord was not affected by adult castration. Thus, the perineal muscles and motoneurons are potential sites of direct CNTF action, and expression of the CNTFRα gene is modulated by androgen, especially in the androgen-sensitive perineal muscles. Transient up-regulation of CNTFRα following castration or androgen receptor blockade may represent a protective response designed to counteract the muscle atrophy normally induced by androgen withdrawal. © 1998 John Wiley & Sons, Inc. J Neurobiol 35: 217–225, 1998     

Effects of dorsal root section and occlusion of dorsal spinal artery on the neurotransmitter candidates in rat spinal cord

In order to obtain further evidence of putative neurotransmitters in primary sensory neurons and interneurons in the dorsal spinal cord, we have studied the effects of unilateral section of dorsal roots and unilateral occlusion of the dorsal spinal artery on cholinergic enzyme activity and on selected amino acid levels in the spinal cord. One week after sectioning dorsal roots from caudal cervical (C₇) to cranial thoracic (T₂) levels, the specific activity of choline acetyltransferase (ChAT) was significantly decreased and acetylcholinesterase (AChE) showed a tendency to decrease in the dorsal quadrant on the operated side of the spinal cord. Dorsal root sectioning had little effect on the levels of free glutamic acid or other amino acids in the dorsal spinal cord. These results suggest that primary sensory neurons may include some cholinergic axons, and that levels of putative amino acid transmitters are not regulated by materials supplied by axonal transport from the dorsal root ganglia. By contrast, one week following unilateral occlusion of the dorsal spinal artery, the activities of ChAT and AChE were unchanged in the operated quadrant of the spinal cord, while decreases of Asp, Glu, and GABA, and an increase in Tau were detected. These findings are consistent with the proposals that such amino acids, but not ACh, may function as neurotransmitter candidates in interneurons of the dorsal spinal cord.Abbreviation used ACh acetylcholine - AChE acetylcholinesterase - Asp aspartic acid - ChAT choline acetyltransferase - GABA -aminobutyric acid - Glu glutamic acid - Gly glycine - SP substance P - Tau taurine     

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.     

Functions and pathophysiological roles of phospholipase D in the brain

Ten years after the isoforms of mammalian phospholipase D (PLD), PLD1 and 2, were cloned, their roles in the brain remain speculative but several lines of evidence now implicate these enzymes in basic cell functions such as vesicular trafficking as well as in brain development. Many mitogenic factors, including neurotransmitters and growth factors, activate PLD in neurons and astrocytes. Activation of PLD downstream of protein kinase C seems to be a required step for astroglial proliferation. The characteristic disruption of the PLD signaling pathway by ethanol probably contributes to the delay of brain growth in fetal alcohol syndrome. The post-natal increase of PLD activities concurs with synapto- and myelinogenesis in the brain and PLD is apparently involved in neurite formation. In the adult and aging brain, PLD activity has antiapoptotic properties suppressing ceramide formation. Increased PLD activities in acute and chronic neurodegeneration as well as in inflammatory processes are evidently due to astrogliosis and may be associated with protective responses of tissue repair and remodeling. ARF-regulated PLD participates in receptor endocytosis as well as in exocytosis of neurotransmitters where PLD seems to favor vesicle fusion by modifications of the shape and charge of lipid membranes. Finally, PLD activities contribute free choline for the synthesis of acetylcholine in the brain. Novel tools such as RNA interference should help to further elucidate the roles of PLD isoforms in brain physiology and pathology.     

依托咪酯对成年大鼠脊髓胶状质局部突触传递的作用

应用盲插全细胞膜片钳技术,在成年大鼠脊髓薄片上观察依托咪酯(etomidate,ET)对脊髓胶状质局部突触传递的影响。实验结果显示,在钳制电压为-70mV时,500μmol/L的ET对微小兴奋性突触后电流(mEPSC)的持续时间、频率和幅度都无明显的作用。在钳制电压为0mV时,50μmol/L的ET使GABA能微小抑制性突触后电流(mIPSC)的持续时间延长45.57±12.46%(P<0.05),但对其频率和幅度无影响。同样在钳制电压为0mV的情况下,50μmol/L的ET对甘氨酸能mIPSC的持续时间、频率及幅度均无作用。以上结果表明,在成年大鼠的脊髓胶状质,ET主要通过延长GABA能mIPSC的持续时间,即延长受体通道的开放时间发挥作用,ET对于兴奋性的突触传递没有直接的作用。     

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.