Dorsal Translocation Research Articles

Modified penile reconstruction in classic bladder exstrophy: Can complete corporal covering of the urethral closure be achieved using incomplete disassembly technique?

To answer the question of whether it is possible to achieve complete corporal covering of the urethral closure using incomplete penile disassembly in classic bladder exstrophy. We hypothesize that mobilization of the corpora under Buck's fascia, their dorsal translocation through the incisions in Buck's fascia and suturing corporal convex sides above the urethra would allow extend corporal covering of the urethra, reducing the risk of urethra-cutaneous fistula formation. A prospective follow-up on all boys who underwent the modified Cantwell-Ransley primary penile reconstruction was conducted. Inclusion criteria comprised bladder exstrophy closure in our institution, ensuring a postoperative follow-up period of no less than 24 months. The key innovation of the technique lies in a deep dissection of the dependent corpora under Buck's fascia, followed by their dorsal relocation through extended dorsal incisions in Buck's fascia, and limited external corporal rotation 90 degrees only at the base of the penis. Between November 2019 and March 2022, 18 boys aged 11 to 35 months met the inclusion criteria and underwent the modified penile reconstruction. Surgical procedures and postoperative period did not include any major complications. Total corporal covering of the urethral sutures was achieved in 15 of 18 patients. No urethra-cutaneous fistulas were observed within 2 years of follow-up. All individuals demonstrated spontaneous erections, and the absence of dorsal curvature was documented. The modified technique of incomplete penile disassembly applied in a homogenous group of patients with classic bladder exstrophy allows penile shaft elongation, improved aesthetic outcomes, preserved erections, and eliminates dorsal curvature. The technique demonstrated feasibility and reliability while maintaining positive effects on tissue circulation. The absence of urethra-cutaneous fistulae is attributed to the complete corporal covering of the urethral sutures and supports the initial hypothesis.

Extensor Carpi Ulnaris “Turn Around” Ligamentoplasty For Distal Radioulnar Joint Instability

Extensor Carpi Ulnaris “Turn Around” Ligamentoplasty For Distal Radioulnar Joint Instability

SpRab11a-Regulated Exosomes Inhibit Bacterial Infection through the Activation of Antilipopolysaccharide Factors in Crustaceans.

Exosomes, secreted by most cells, are critical antimicrobial immune factors in animals. Recent studies of certain key regulators of vesicular transport, the Rab GTPases, have linked Rab dysfunction to regulation of innate immune signaling. However, the relationship between exosomes and Rab GTPases, resulting in antimicrobial activity in vertebrates and invertebrates during pathogenic infection, has not been addressed. In this study, SpRab11a was reported to have a protective effect on the survival rate of mud crabs Scylla paramamosain after Vibrio parahaemolyticus challenge through the stimulation of exosome secretion and modulation of anti-LPS factor (ALF) expression. Furthermore, Sp14-3-3 was confirmed to be densely packaged in exosomes after V. parahaemolyticus infection, which could recruit the MyD88 and TLR by binding the Toll/IL-1R domain to the plasma membrane, promoting the translocation of Dorsal from the cytoplasm into the nucleus, and thereby regulating ALFs expression in the hemocytes of mud crab in response to the bacterial infection. The findings therefore provide, to our knowledge, a novel mechanism that underlies the cross-talk between SpRab11a-regulated exosome formation and ALFs expression in innate immune response in invertebrates, with a crustacean species, mud crab S. paramamosain, as a model study.

Ftz-F1H promotes white spot syndrome virus infection in shrimp by suppressing the Dorsal pathway

White spot syndrome virus (WSSV) is currently a major viral pathogen of cultured shrimp. The NF-κB signaling is central to the regulation of immune responses in both invertebrates and vertebrates. Dorsal is a member of the NF-κB family in arthropods, playing important role in shrimp antiviral response. The fushi tarazu (FTZ) transcription factor (Ftz-F1) homologue (Ftz-F1H) is a novel identified orphan nuclear receptor in Pacific white shrimp Penaeus vannamei with an inhibitory effect on anti-Vibrio parahaemolyticus response. The current study investigated the role of Ftz-F1H in the immune response against WSSV infection. We showed that Ftz-F1H directly promoted the expression of Cactus, the cytoplasmic inhibitor of the Dorsal pathway in shrimp, and inhibited the nuclear translocation of Dorsal. Silencing of Ftz-F1H in vivo suppressed the WSSV infection in shrimp. These suggested that Ftz-F1H could promote WSSV infection by inhibiting the activation of the Dorsal pathway. This study, together with the previous finding, indicated that inhibition of Ftz-F1H in shrimp could enhance the defense against both bacterial and viral infections.

Activation of Toll Pathway Is Different between Kuruma Shrimp and Drosophila

The Toll pathway is essential for inducing an immune response to defend against bacterial invasion in vertebrates and invertebrates. Although Toll receptors and the transcription factor Dorsal were identified in different shrimp, relatively little is known about how the Toll pathway is activated or the function of the pathway in shrimp antibacterial immunity. In this study, three Tolls (Toll1–3) and the Dorsal were identified in Marsupenaeus japonicus. The Toll pathway can be activated by Gram-positive (G+) and Gram-negative (G−) bacterial infection. Unlike Toll binding to Spätzle in Drosophila, shrimp Tolls could directly bind to pathogen-associated molecular patterns from G+ and G− bacteria, resulting in Dorsal translocation into nucleus to regulate the expression of different antibacterial peptides (AMPs) in the clearance of infected bacteria. These findings suggest that shrimp Tolls are pattern recognition receptors and the Toll pathway in shrimp is different from the Drosophila Toll pathway but identical with the mammalian Toll-like receptor pathway in its activation and antibacterial functions.

β-Arrestins Negatively Regulate the Toll Pathway in Shrimp by Preventing Dorsal Translocation and Inhibiting Dorsal Transcriptional Activity

The Toll signaling pathway plays an important role in the innate immunity ofDrosophila melanogasterand mammals. The activation and termination of Toll signaling are finely regulated in these animals. Although the primary components of the Toll pathway were identified in shrimp, the functions and regulation of the pathway are seldom studied. We first demonstrated that the Toll signaling pathway plays a central role in host defense againstStaphylococcus aureusby regulating expression of antimicrobial peptides in shrimp. We then found that β-arrestins negatively regulate Toll signaling in two different ways. β-Arrestins interact with the C-terminal PEST domain of Cactus through the arrestin-N domain, and Cactus interacts with the RHD domain of Dorsal via the ankyrin repeats domain, forming a heterotrimeric complex of β-arrestin·Cactus·Dorsal, with Cactus as the bridge. This complex prevents Cactus phosphorylation and degradation, as well as Dorsal translocation into the nucleus, thus inhibiting activation of the Toll signaling pathway. β-Arrestins also interact with non-phosphorylated ERK (extracellular signal-regulated protein kinase) through the arrestin-C domain to inhibit ERK phosphorylation, which affects Dorsal translocation into the nucleus and phosphorylation of Dorsal at Ser(276)that impairs Dorsal transcriptional activity. Our study suggests that β-arrestins negatively regulate the Toll signaling pathway by preventing Dorsal translocation and inhibiting Dorsal phosphorylation and transcriptional activity.

Toll pathway modulates TNF-induced JNK-dependent cell death in Drosophila.

Signalling networks that control the life or death of a cell are of central interest in modern biology. While the defined roles of the c-Jun N-terminal kinase (JNK) pathway in regulating cell death have been well-established, additional factors that modulate JNK-mediated cell death have yet to be fully elucidated. To identify novel regulators of JNK-dependent cell death, we performed a dominant-modifier screen in Drosophila and found that the Toll pathway participates in JNK-mediated cell death. Loss of Toll signalling suppresses ectopically and physiologically activated JNK signalling-induced cell death. Our epistasis analysis suggests that the Toll pathway acts as a downstream modulator for JNK-dependent cell death. In addition, gain of JNK signalling results in Toll pathway activation, revealed by stimulated transcription of Drosomycin (Drs) and increased cytoplasm-to-nucleus translocation of Dorsal. Furthermore, the Spätzle (Spz) family ligands for the Toll receptor are transcriptionally upregulated by activated JNK signalling in a non-cell-autonomous manner, providing a molecular mechanism for JNK-induced Toll pathway activation. Finally, gain of Toll signalling exacerbates JNK-mediated cell death and promotes cell death independent of caspases. Thus, we have identified another important function for the evolutionarily conserved Toll pathway, in addition to its well-studied roles in embryonic dorso-ventral patterning and innate immunity.

Measurement and Evaluation of the Alar Base in Unilateral Secondary Lip Nasal Deformities by Three-Dimensional Computed Tomography

Objective : This study aimed to analyze the asymmetry of the pyriform aperture and alar base in patients with unilateral secondary nasal deformities by three-dimensional computed tomography (3D-CT). Methods : 3D-CT images of the subject group of 101 adult patients and of a control group of 65 normal adults were examined. Sixty-nine patients without alveolar bone grafting (ABG) were classified as Group A, and 32 patients with ABG were classified as Group B. Seven landmarks (INM, LPA, IPA, Gbase, Gsup, Glat, and Sbal) were measured for both the subject and control groups, and comparative analyses were done to assess the degree of asymmetry in the subject group. Results : For over 95% of Group A and 80% to 85% of Group B, the index of LPA and IPA showed asymmetry or marked asymmetry. The index of Gbase, Glat, Gsup, and Sbal showed symmetry for around 50% of Group A and about 60% of Group B. In Group A, dorsal, lateral, and caudal translocation was found on the cleft side in LPA and IPA, while all soft landmarks showed dorsal translocation. In Group B, caudal translocation was found in both LPA and IPA, but only LPA appeared dorsal on the cleft side, while Glat showed dorsal and caudal translocation. Conclusion : The results indicated that the degree of asymmetry of hard tissue landmarks far exceeded that of the soft tissue landmarks, and the degree of asymmetry of pyriform aperture was higher than expected for patients after ABG.

The maternal JAK/STAT pathway of Drosophila regulates embryonic dorsal-ventral patterning

Activation of NFkappaB plays a pivotal role in many cellular processes such as inflammation, proliferation and apoptosis. In Drosophila, nuclear translocation of the NFkappaB-related transcription factor Dorsal is spatially regulated in order to subdivide the embryo into three primary dorsal-ventral (DV) domains: the ventral presumptive mesoderm, the lateral neuroectoderm and the dorsal ectoderm. Ventral activation of the Toll receptor induces degradation of the IkappaB-related inhibitor Cactus, liberating Dorsal for nuclear translocation. In addition, other pathways have been suggested to regulate Dorsal. Signaling through the maternal BMP member Decapentaplegic (Dpp) inhibits Dorsal translocation along a pathway parallel to and independent of Toll. In the present study, we show for the first time that the maternal JAK/STAT pathway also regulates embryonic DV patterning. Null alleles of loci coding for elements of the JAK/STAT pathway, hopscotch (hop), marelle (mrl) and zimp (zimp), modify zygotic expression along the DV axis. Genetic analysis suggests that the JAK kinase Hop, most similar to vertebrate JAK2, may modify signals downstream of Dpp. In addition, an activated form of Hop results in increased levels of Cactus and Dorsal proteins, modifying the Dorsal/Cactus ratio and consequently DV patterning. These results indicate that different maternal signals mediated by the Toll, BMP and JAK/STAT pathways may converge to regulate NFkappaB activity in Drosophila.

Hemolymph‐dependent and ‐independent responses in Drosophila immune tissue

Insects possess an antimicrobial defense response that is similar to the mammalian innate immune response. The innate immune system is designed to recognize conserved components of microorganisms called pathogen-associated molecular patterns (PAMPs). How host receptors detect PAMPs and transmit the signals to mount the immune response is being elucidated. Using GFP-Dorsal, -Dif, and -Relish reporter proteins in ex vivo assays, we demonstrate that Drosophila fat bodies, a major immune tissue, have both hemolymph-dependent and -independent responses. Microbial preparations such as lipoteichoic acid (LTA) and peptidoglycan (PGN) can stimulate some responses from dissected and rinsed larval fat bodies. Therefore, at least some aspects of recognition can occur on fat body cell surfaces, bypassing the requirement of hemolymph. Our results also show that supernatants from bacterial cultures can stimulate the nuclear translocation of Dorsal in dissected fat bodies, but this stimulation is strictly hemolymph-dependent. Various biochemical assays suggest that the factors from bacterial supernatants that stimulate the hemolymph-dependent nuclear translocation are likely made up of proteins. We further show that Dorsal mutant larvae have much lower phenoloxidase activity, consistent with a more important role of Dorsal in innate immunity than previously shown.

The Drosophila atypical protein kinase C-ref(2)p complex constitutes a conserved module for signaling in the toll pathway.

Recent results showed the critical role of the mammalian p62-atypical protein kinase C (aPKC) complex in the activation of NF-kappaB in response to different stimuli. Here we demonstrate using the RNA interference technique on Schneider cells that the Drosophila aPKC (DaPKC) is required for the stimulation of the Toll-signaling pathway, which activates the NF-kappaB homologues Dif and Dorsal. However, DaPKC does not appear to be important for the other Drosophila NF-kappaB signaling cascade, which activates the NF-kappaB homologue Relish in response to lipopolysaccharides. Interestingly, DaPKC functions downstream of the nuclear translocation of Dorsal or Dif, controlling the transcriptional activity of the Drosomycin promoter. We also show that the Drosophila Ref(2)P protein is the homologue of mammalian p62 as it binds to DaPKC, its overexpression is sufficient to activate the Drosomycin but not the Attacin promoter, and its depletion severely impairs Toll signaling. Collectively, these results demonstrate the conservation of the p62-aPKC complex for the control of innate immunity signal transduction in Drosophila melanogaster.

Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein.

Recognition of pathogens by Drosophila Toll or human Toll-like receptors results in translocation of Dorsal or its human homologue NF-kappaB, respectively; in Drosophila, this is followed by the production of antimicrobial peptides serving as antimicrobial effector system of the innate immune response. We investigated whether human Toll-like receptors also mediate induction of the synthesis of antimicrobial peptides. We found that HEK293 cells transfected with Toll-like receptor 2, but not wild-type cells responded to stimulation with bacterial lipoprotein by production of human beta-defensin 2. Furthermore, the human lung epithelial cell line A549 was found to constitutively express Toll-like receptor 2 and to produce beta-defensin 2 in response to bacterial lipoprotein. This response was abrogated by blocking the signaling pathway activated through Toll-like receptors by transfecting the A549 cells with a dominant-negative form of IRAK-2. Thus, exposure of human cells to bacterial lipoprotein elicits production of the antimicrobial peptide beta-defensin 2 through Toll-like receptor 2.

Dorsal downregulation of GSK3beta by a non-Wnt-like mechanism is an early molecular consequence of cortical rotation in early Xenopus embryos.

Cortical rotation and concomitant dorsal translocation of cytoplasmic determinants are the earliest events known to be necessary for dorsoventral patterning in Xenopus embryos. The earliest known molecular target is beta-catenin, which is essential for dorsal development and becomes dorsally enriched shortly after cortical rotation. In mammalian cells cytoplasmic accumulation of beta-catenin follows reduction of the specific activity of glycogen synthase kinase 3-beta (GSK3beta). In Xenopus embryos, exogenous GSK3beta) suppresses dorsal development as predicted and GSK3beta dominant negative (kinase dead) mutants cause ectopic axis formation. However, endogenous GSK3beta regulation is poorly characterized. Here we demonstrate two modes of GSK3beta regulation in Xenopus. Endogenous mechanisms cause depletion of GSK3beta protein on the dorsal side of the embryo. The timing, location and magnitude of the depletion correspond to those of endogenous beta-catenin accumulation. UV and D(2)O treatments that abolish and enhance dorsal character of the embryo, respectively, correspondingly abolish and enhance GSK3beta depletion. A candidate regulator of GSK3beta, GSK3-binding protein (GBP), known to be essential for axis formation, also induces depletion of GSK3beta. Depletion of GSK3beta is a previously undescribed mode of regulation of this signal transducer. The other mode of regulation is observed in response to Wnt and dishevelled expression. Neither Wnt nor dishevelled causes depletion but instead they reduce GSK3beta-specific activity. Thus, Wnt/Dsh and GBP appear to effect two biochemically distinct modes of GSK3beta regulation.

Neurons expressing NADPH-diaphorase in the developing human spinal cord.

The present study used nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry to identify populations of neurons containing nitric oxide synthase and to describe their putative migration during development of the human spinal cord. As early as week 6 (W6) of gestation, diaphorase expression was observed in sympathetic preganglionic neurons (SPNs) and interneurons of the ventral horn. As development proceeded, the SPNs translocated dorsally to form the intermediolateral nucleus, and the interneurons remained scattered throughout the ventral horn. In addition to the dorsal translocation of SPNs, a unique dorsomedially directed migratory pathway was observed. At later stages of development, other groups of SPNs were identified laterally in the lateral funiculus and medially in the intercalated and central autonomic regions. In addition, two "U-shaped" groups of diaphorase-labeled cells were identified around the ventral ventricular zone at W7. Cells of these groups appeared to translocate dorsally over the next weeks and presumably give rise to interneurons within the deep dorsal horn and surrounding the central canal. Furthermore, during W7-14 of gestation, the deep dorsal horn contained a number of diaphorase-positive cells, whereas the superficial dorsal horn was relatively free of staining. These data demonstrate that nitric oxide is present very early in human spinal cord development and that two unique cell migrations initially observed in rodents have now been identified in humans. Furthermore, nitric oxide may be expressed in some populations of neurons as they migrate to their final positions, suggesting that this molecule may play a role in neuronal development.

The treatment of wrist instability.

The concept of carpal instability has evolved considerably over the past few years. Initially, the term ‘instability’ was considered to be synonymous with ‘malalignment’. A wrist was regarded as unstable when there was an alteration of the sagittal and/or anteroposterior alignment of the carpal bones beyond what was judged to be normal. Based on this, four major types of carpal malalignment were recognised: Dorsal intercalated segment instability (DISI). The lunate, regarded as an intercalated segment between the distal row and the forearm bones, is abnormally extended relative to its proximal and distal links. Volar intercalated segment instability (VISI). In the sagittal plane the lunate appears abnormally flexed. Ulnar translocation. The proximal row is abnormally displaced (rotated or translocated) relative to the radius in an ulnar direction. Dorsal translocation. Due to a malunited fracture of the radius, the carpus is subluxed in a dorsal direction. These four types of instability could therefore always be diagnosed by plain radiography. A number of authors including Schernberg and Zdravkovic, Jacob and Sennwald have criticised this concept of instability since not every alteration of carpal alignment is pathological. Wrists showing congenital hyperlaxity often appear to be grossly malaligned and yet are frequently asymptomatic. These patients are able to cope effectively with most activities of daily living and seldom require treatment. It was therefore necessary to reconsider the definition of instability and exclude those patients whose carpal malalignment is simply a variation of the normal. As a result, instability has been redefined as the inability to bear physiological loads with an associated loss of the normal carpal alignment. This definition again was felt to be inadequate since it excludes those patients whose wrist is asymptomatic for most of the time, is well aligned and able to sustain physiological loads, but becomes painful only when performing a specific task, such as opening a jar or lifting heavy objects, with a typical sensation of ‘giving way’. It is apparent that there is dynamic instability, occurring when carpal malalignment appears sporadically under certain loading conditions, and static instability when malalignment is permanent regardless of the amount of load being applied. By admitting differences in the severity of injuries producing carpal instability, some of the problems of definition were solved. Nevertheless, some concerns remained. By defining stability in terms of ‘ability to bear load’, the impression was gained that there was a problem only of load transfer (kinetic dysfunction) rather than of both load and movement (kinetic and kinematic dysfunction). For instance, a wrist with an old carpal collapse and extensive joint degeneration may bear physiological loads despite malalignment. Such cases, however, should be considered as pathologically unstable since their movement cannot be as smooth and well co-ordinated as that of a normally functioning wrist. To fulfil these biomechanical criteria of stability, a normal wrist must be able to maintain a balance between the articulating bones in both kinetic and kinematic terms under physiological loads, through the whole range of movement. The term instability must be interpreted as ‘carpal dysfunction’, which implies that in a normal wrist there is the ability to transfer loads without sudden changes of stress on the articular cartilage (normal kinetics) and the capacity to move throughout the normal range without sudden alterations of intercarpal alignment (normal kinematics).

Cactus protein degradation mediates Drosophila dorsal-ventral signaling.

Dorsal-ventral patterning in the Drosophila embryo relies on a signal transduction pathway that is similar to a signaling pathway leading to the activation of the mammalian transcription factor NF-kappa B. Stimulation of this Drosophila pathway on the ventral side of the embryo causes the nuclear translocation of Dorsal, the Drosophila NF-kappa B homolog. Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. We show that Cactus, like I kappa B, is rapidly degraded in response to signaling. More importantly, signal-dependent degradation of Cactus does not require the presence of Dorsal, indicating that Cactus degradation is a direct response to signaling, and that disruption of the Dorsal/Cactus complex is a secondary result of Cactus degradation. Mutant alleles of cactus that encode more stable forms of the protein block signaling, showing that efficient degradation is necessary for signaling. We find that Cactus protein stability is regulated by two independent processes that rely on different regions within the protein: signal-dependent degradation requires sequences in the amino terminus or ankyrin repeats, whereas signal-independent degradation of free Cactus requires the carboxy-terminal region of the protein that includes a PEST sequence.

Preganglionic autonomic motor neurons display normal translocation patterns in slice cultures of embryonic rat spinal cord

Phenotypic differences between somatic and autonomic motor neurons (SMNs and AMNs, respectively) may be modulated by epigenetic factors during the histogenic migrations of these cells. In order to study this problem experimentally, we have developed an in vitro, organotypic slice preparation of embryonic rat spinal cord. Our main objectives for this preparation were to determine whether in vivo patterns of motor neuronal translocations were mimicked in vitro, and, if they were, to begin to analyze such movements with experimental procedures that cannot be applied to the study of mammalian spinal cord development in vivo. Using a modification of existing organotypic slice procedures, we have shown that ChAT, an axonal surface glycoprotein and a low-molecular-weight neurofilament protein are expressed in slices cultured for up to 21 d, thus indicating that spinal neurons remained viable in vitro for relatively long periods. Most importantly, retrograde labeling and subsequent confocal microscopy have shown that the SMNs and AMNs of the slice preparations become segregated ventrodorsally into two distinct subcolumns as seen in vivo. The formation of separate AMN and SMN subcolumns appears to result from a dorsal translocation of AMNs. The fact that this cellular movement occurs in the slice preparation has allowed us to follow this phenomenon directly within the same specimen over a period of days. In addition, we have been able to observe the translocation of AMNs following the removal of their peripheral synaptic targets. The results of these experiments provide further evidence that AMNs undergo a dorsal translocation during the course of spinal cord development, and that this cellular movement may be due to an active migration. They also indicate that AMN movement is not dependent upon continual connection of these neurons with the paravertebral sympathetic ganglia.

Embryonic development of rat sympathetic preganglionic neurons: possible migratory substrates.

Spinal somatic and autonomic (sympathetic preganglionic) motor neurons are generated synchronously and, subsequently, migrate from the ventricular zone together to form a common primitive motor column. However, these two subsets of motor neurons ultimately express several phenotypic differences, including somal size, peripheral targets, and spinal cord locations. While somatic motor neurons remain ventrally, autonomic motor neurons (AMNs) move both dorsally and medially between embryonic days 14 and 18, when they approximate their final locations in spinal cord. The goal of the present investigation was to determine the potential guidance substrates available to AMNs during these movements. The dorsal translocation was studied in developing upper thoracic spinal cord, because, at this level, the majority of AMNs are located dorsolaterally. Sections were double-labeled by ChAT (choline acetyltransferase) and SNAP/TAG-1 (stage-specific neurite associated protein/transiently expressed axonal surface glycoprotein) immunocytochemistry to visualize motor neurons and the axons of early forming circumferential interneurons, respectively. Results showed that during the developmental stage when AMNs translocated dorsally, SNAP/TAG-1 immunoreactive lateral circumferential axons were physically located along the borders of the AMN region, as well as among its constituent cells. These findings indicate that lateral circumferential axons, as well as the SNAP/TAG-1 molecules contained upon their surfaces, are in the correct spatial and temporal position to serve as guidance substrates for AMNs. The medial translocation was studied in developing lower thoracic-upper lumbar spinal cord, because, at this level, more than half of the AMNs are medially located. Sections were double-labeled by ChAT and vimentin immunocytochemistry to visualize motor neurons and radial glial fibers, respectively. Observations on consecutive developmental days of the medial translocation revealed that AMNs were aligned with parallel arrays of radial glial fibers. Thus, the glial processes could serve as guides for the AMN medial movement. Future experimental analyses will examine whether circumferential axons and radial glial fibers are in fact functioning as migratory guides during AMN development, and, if so, whether specific surface molecules on these guides trigger the subsequent differentiation of AMNs.

Migration patterns of sympathetic preganglionic neurons in embryonic rat spinal cord

The displacement of immature neurons from their place of origin in the germinal epithelium toward their adult positions in the nervous system appears to involve migratory pathways or guides. While the importance of radial glial fibers in this process has long been recognized, data from recent investigations have suggested that other mechanisms might also play a role in directing the movement of young neurons. We have labeled autonomic preganglionic cells by microinjections of horseradish peroxidase (HRP) into the sympathetic chain ganglia of embryonic rats in order to study the migration and differentiation of these spinal cord neurons. Our results, in conjunction with previous observations, suggest that the migration pattern of preganglionic neurons can be divided into three distinct phases. In the first phase, the autonomic motor neurons arise in the ventral ventricular zone and migrate radially into the ventral horn of the developing spinal cord, where, together with somatic motor neurons, they form a single, primitive motor column (Phelps P. E., Barber R. P., and Vaughn J. E. (1991). J. Comp. Neurol. 307:77-86). During the second phase, the autonomic motor neurons separate from the somatic motor neurons and are displaced dorsally toward the intermediate spinal cord. When the preganglionic neurons reach the intermediolateral (IML) region, they become progressively more multipolar, and many of them undergo a change in alignment, from a dorsoventral to a mediolateral orientation. In the third phase of autonomic motor neuron development, some of these cells are displaced medially, and occupy sites between the IML and central canal. The primary and tertiary movements of the preganglionic neurons are in alignment with radial glial processes in the embryonic spinal cord, an arrangement that is consistent with a hypothesis that glial elements might guide autonomic motor neurons during these periods of development. In contrast, during the second phase, the dorsal translocation of preganglionic neurons occurs in an orientation perpendicular to radial glial fibers, indicating that glial elements are not involved in the secondary migration of these cells. The results of previous investigations have provided evidence that, in addition to glial processes, axonal pathways might provide a substrate for neuronal migration. Logically, therefore, it is possible that the secondary dorsolateral translocation of autonomic preganglionic neurons could be directed along early forming circumferential axons of spinal association interneurons, and this hypothesis is supported by the fact that such fibers are appropriately arrayed in both developmental time and space to guide this movement.

Results of surgical treatment of painful neuromas of the hand

The surgical treatment of 50 patients with 101 neuromas over the last 10 years is reported. Simple excision and implantation into local muscle resulted in an unacceptable reoperative rate of 65%. Ray amputation for symptomatic neuromas resulted in the highest reoperation rate but resulted in little or no subjective improvement. There appears to be a correlation between delayed healing after the initial injury and the severity of neuroma symptoms. Dorsal translocation of the neuroma consistently resulted in decreased sensitivity without longterm recurrence.