Vertebrate Peripheral Nervous System Research Articles

Who Are You Calling a Squirt?

An enduring mystery that has captivated generations of scientists is the question of humanity's evolutionary origins. It's thought that complicated and specialized creatures such as ourselves evolved from much simpler ancestors by co-opting and elaborating upon genes, proteins, and tissue arrangements pioneered by more-primitive organisms. If that's so, then we should be able to see features reminiscent of ourselves in creatures that look very little like us. Scientists studying tunicates (sea squirts) have demonstrated several ways in which these organisms can inform us about our own developmental and evolutionary origins. Tunicates are an ancient life form, with fossils dating back to the Neoproterozoic era (542–1,000 million years ago). These marine organisms start out as embryos, then develop into a mobile tadpole form (complete with a brain-equivalent and a tail with a nerve cord and a stiff notochord that functions like a spine) that swims around looking for a substrate to attach to. Once attached, the tail is reabsorbed and the animal assumes a tube-like shape covered in a strong but flexible “tunic.” To get a better understanding of the molecular events that underlie the development of the vertebrate peripheral nervous system (PNS)—neural structures outside the brain that are important for sensing the environment—Andrea Pasini, Sebastien Darras, and colleagues undertook a systematic characterization of the early developmental events that produce the tunicate tadpole PNS. To do this, they went all the way back to the fertilized egg to examine the origins of cells that contribute to the physical structures of the tadpole tail. With their tadpole tail and spinal-like structures, tunicates are the distant cousins of vertebrates like ourselves. Following fertilization and three rounds of cell division, which create an eight-cell embryo, two of these eight cells (designated “b4.2”) will ultimately give rise to all the cells that contribute to the external tissues of the tail, including the animal's epidermis and ciliated caudal epidermal sensory neurons (CESNs) of the PNS. By the time the embryo has divided to the size of 110 cells, each b4.2 cell has given rise to 16 cells (called b-line cells). The researchers first looked to see which of these b-line cells contributed to what parts of the tail by labeling individual cells with a fluorescent dye at the 110-cell stage and then looking at the embryos again once tail development was complete. This revealed a remarkably regular organization of the tail epidermis, subdivided into midline, mediolateral and lateral territories, each originating from mostly distinct precursors. In particular, they find that cells that contribute to the dorsal and ventral midline tissues give rise to both epidermis and CESNs. Pasini et al. found that two secreted factors, fibroblast growth factor (FGF) and bone morphogenetic protein (BMP), respectively specify the dorsal and ventral midline identity of b4.2-derived cells during the first eight hours of development. Interestingly, both FGF and BMP are also involved in the formation of the midline epidermal territories in vertebrates. Once the midline territories are specified, the embryo needs to select among these cells the minority that will form epidermal neurons. In other animals, one pathway that governs the generation of two different cell fates in neighboring cells that derive from a common progenitor cell is the Notch pathway. Indeed, when Pasini et al. looked in tunicates, they found evidence that the Notch pathway controls the number of CESNs that are produced in dorsal and ventral midline tissues. Taken together, the study provides a molecular framework explaining how the embryo sequentially specifies first a bipotential population of cells in the midline epidermis, and then selects among these cells those that will adopt a neuronal fate. Pasini et al. say that their observations in tunicates can pave the way to a better understanding of how analogous structures form in higher animals; some of the pathways and signaling molecules at work here appear to play similar roles in the development of the vertebrate neural plate border but also, and more unexpectedly, in the formation of the median fin that allows the animal to swim. Thus, the common ancestor of tunicates and vertebrates may have coupled the formation of the fin and its sensory innervation, a coupling lost in modern vertebrates but which remains in the tunicates. Several questions remain to be clarified in this work; for example, the authors still don't know whether FGF, BMP, or Notch directly control cell-fate decisions, or whether intermediate signaling pathways may be involved. However, they have plenty of precedents to rely on in tracking down the answers to these questions; some of the first insights in experimental embryology came from Laurent Chabry's work in tunicates in 1888, and it is inspiring to think of how much we still have to learn from this animal.

The presence of a galanin-like peptide in the gut neuroendocrine system of Lampetra fluviatilis and Acipenser transmontanus: an immunohistochemical study

Galanin is a brain-gut neuropeptide present in the central and peripheral nervous systems of vertebrates. In the present survey, the galaninergic and the diffuse endocrine systems of the alimentary canal of the river lamprey, Lampetra fluviatilis, and the white sturgeon, Acipenser transmontanus, were studied by immunohistochemistry. The results show the presence of galanin-like immunoreactive endocrine cells in the gut of L. fluviatilis. In addition, a galanin-like immunoreactivity was detected in enteric intramural neurons of both species. It is conceivable that the galaninergic system plays in both species a role in the regulation of the gut muscle contractility and in the modulation of mucosal secretive/absorptive processes. In A. transmontanus, the presence of galanin-like immunoreactive nerve fibres associated with components of the gut associated-lymphoid tissue is possibly correlated with a control of the defensive events at this site. The presence of a galanin-like immunoreactivity in the neuroendocrine system of these two ancient fishes confirms the hypothesis on the early occurrence of this regulative molecule in the gastro-enteric system of vertebrates.

Regulatory mechanisms that govern nicotinic synapse formation in neurons.

Individual cholinoceptive neurons express high levels of different neuronal nicotinic acetylcholine receptor (nAChR) subtypes, and target them to the appropriate synaptic regions for proper function. This review focuses on the intercellular and intracellular processes that regulate nAChR expression in vertebrate peripheral nervous system (PNS) and central nervous system (CNS) neurons. Specifically, we discuss the cellular and molecular mechanisms that govern the induction and maintenance of nAChR expression-innervation, target tissue interactions, soluble factors, and activity. We define the regulatory principles of interneuronal nicotinic synapse differentiation that have emerged from these studies. We also discuss the molecular players that target nAChRs to the surface membrane and the interneuronal synapse.

Towards crystallization of hydrophobic myelin glycoproteins: P0 and PASII/PMP22

The preparation of a pure and homogeneous protein sample at proper concentration is a prerequisite for success when attempting their crystallization for structural determination. The detergents suitable for solubilization particularly of membrane proteins are not always the best for crystallization. Myelin of the peripheral nervous system of vertebrates is the example of a membrane for which neutral or “gentle” detergents are not even strong enough to solubilize its proteins. In contrast, sodium- or lithium-dodecyl sulfate is very effective. We solubilized myelin membrane in 2% (w/v) sodium dodecyl sulfate, followed by chromatographic purification of the hydrophobic myelin glycoproteins P0 and PASII/PMP22, and finally, we have exchanged the sodium dodecyl sulfate bound to protein for other neutral detergents using ceramic hydroxyapatite column. Theoretically, we should easily exchange sodium dodecyl sulfate for any neutral detergent, but for some of them, the solubility of myelin glycoproteins is low. To monitor the potential variability in the secondary structure of glycoproteins, we have used circular dichroism. Sodium dodecyl sulfate seems to be the appropriate detergent for the purpose of purification of very hydrophobic glycoproteins, since it can be easily exchanged for another neutral detergent.

Migration and Function of a Glial Subtype in the Vertebrate Peripheral Nervous System

Glia-axon interactions are essential for the development and function of the nervous system. We combine in vivo imaging and genetics to address the mechanism by which the migration of these cells is coordinated during embryonic development. Using stable transgenic lines, we have followed the migration of one subset of glial cells and their target axons in living zebrafish embryos. These cells coalesce at an early stage and remain coupled throughout migration, with axons apparently pathfinding for glia. Mutant analysis demonstrates that axons provide instructive cues that are sufficient to control glial guidance. Furthermore, mutations in the transcription factor Sox10/ cls uncouple the migration of axons and glia. Finally, genetic ablation of this glial subtype reveals an essential role in nerve fasciculation.

The early life of a Schwann cell.

Schwann cells are the major glial population of the vertebrate peripheral nervous system. In the adult, they build a protecting sheath around neuronal processes and myelinate large-caliber axons. Already early in development, Schwann cells and neurons establish close contacts. Later development and the maintenance of peripheral nerves are crucially dependent on the controlled bi-directional dialogue between these two cell types. Several major phases can be distinguished in the life of a Schwann cell: determination, differentiation, and potentially myelination. The aim of this review is to summarize the molecular and cellular characteristics of the first steps in the life of a Schwann cell, the development from a multipotent neural crest cell to a differentiated Schwann cell.

Sympathetic neuronal survival induced by retinal trophic factors.

Neuronal survival in the vertebrate peripheral nervous system depends on neurotrophic factors available from target tissues. In an attempt to identify novel survival factors, we have studied the effect of secreted factors from retinal cells on the survival of chick sympathetic ganglion neurons. Embryonic day 10 sympathetic neurons undergo programmed cell death after 48 h without appropriate levels of nerve growth factor (NGF). Retina Conditioned Media (RCM) from explants of embryonic day 11 retinas maintained for 4 days in vitro supported 90% of E10 chick sympathetic neurons after 48 h. Conditioned medium from purified chick retinal Muller glial cells supported nearly 100% of E10 chick sympathetic neurons. Anti-NGF (1 microg/mL) blocked the survival effect of NGF, but did not block the trophic effect of RCM. Neither BDNF nor NT4 (0.1-50 ng/mL) supported E10 sympathetic neuron survival. Incubation of chimeric immunoglobulin-receptors TrkA, TrkB, or TrkC had no effect on RCM-induced sympathetic neuron survival. The survival effects were not blocked by anti-GDNF, anti-TGFbeta, and anti-CNTF and were not mimicked by FGFb (0.1-10 nM). LY294002 at 50 microM, but not PD098059 blocked sympathetic survival induced by RCM. Further, the combination of RCM and NGF did not result in an increase in neuronal survival compared with NGF alone (82% survival after 48 h). The secreted factor in RCM is retained in subfractions with a molecular weight above 100 kDa, binds to heparin, and is unaffected by dialysis, but is heat sensitive. Our results indicate the presence of a high-molecular weight retinal secreted factor that supports sympathetic neurons in culture.

Decreased S100-beta protein in schizophrenia: preliminary evidence

The S100 proteins are a family of calcium-binding proteins found in the central and peripheral nervous systems of vertebrates. S100β, the most abundant member of this family in the CNS, mediates calcium signal transduction, and shows neurotrophic, gliotrophic and mitogenic actions that influence the development and maintenance of the nervous system. Another member of the S100 family (S100A10) was found to modulate phospholipid turnover by inhibiting the activity of enzyme phospholipase A2 (PLA2). We determined the concentration of S100β protein in the plasma of 23 medicated schizophrenic patients and 23 healthy controls. S100β protein accounts for 96% of the total S100 in the brain. Schizophrenic patients showed reduced S100β concentrations ( p=0.003), and this finding was not related to clinical variables or to intake of antipsychotic medication. Decreased S100β could be related to the findings of increased PLA2 activity and to brain maldevelopment in schizophrenia. These results are discussed further with respect to the role of adenosine in S100β release.

Expression of frequenin at the frog ( Rana) neuromuscular junction, muscle spindle and nerve

Frequenin is a calcium binding protein previously implicated in the regulation of neurotransmission in Drosophila and Xenopus. We have used the frog ( Rana pipiens) to study the localization and regulation of expression of frequenin-like molecules in the vertebrate peripheral nervous system. Affinity purified antibodies to frequenin recognize molecules in the neuromuscular junction, axons in the peripheral nerve, and neuronal processes in muscle spindles. Western blots of endplate regions, peripheral nerve, and brain, resulted in the labelling of a single 24 kDa band, which is the expected size for frequenin. These results suggest that frequenin expression is high in the frog peripheral nervous system, and may reflect a function for frequenin in synaptic transmission in vertebrates.

Spinal motor axons and neural crest cells use different molecular guides for segmental migration through the rostral half-somite

The peripheral nervous system in vertebrates is composed of repeating metameric units of spinal nerves. During development, factors differentially expressed in a rostrocaudal pattern in the somites confine the movement of spinal motor axons and neural crest cells to the rostral half of the somitic sclerotome. The expression patterns of transmembrane ephrin-B ligands and interacting EphB receptors suggest that these proteins are likely candidates for coordinating the segmentation of spinal motor axons and neural crest cells. In vitro, ephrin-B1 has indeed been shown to repel axons extending from the rodent neural tube (Wang & Anderson, 1997). In avians, blocking interactions between EphB3 expressed by neural crest cells and ephrin-B1 localized to the caudal half of the somite in vivo resulted in loss of the rostrocaudal patterning of trunk neural crest migration (Krull et al., 1997). The role of ephrin-B1 in patterning spinal motor axon outgrowth in avian embryos was investigated. Ephrin-B1 protein was found to be expressed in the caudal half-sclerotome and in the dermomyotome at the appropriate time to interact with the EphB2 receptor expressed on spinal motor axons. Treatment of avian embryo explants with soluble ephrin-B1, however, did not perturb the segmental outgrowth of spinal motor axons through the rostral half-somite. In contrast, under the same treatment conditions with soluble ephrin-B1, neural crest cells migrated aberrantly through both rostral and caudal somite halves. These results indicate that the interaction between ephrin-B1 and EphB2 is not required for patterning spinal motor axon segmentation. Even though spinal motor axons traverse the same somitic pathway as neural crest cells, different molecular guidance mechanisms appear to influence their movement. © 2000 John Wiley & Sons, Inc. J Neurobiol 43: 437–447, 2000

Spinal motor axons and neural crest cells use different molecular guides for segmental migration through the rostral half-somite

The peripheral nervous system in vertebrates is composed of repeating metameric units of spinal nerves. During development, factors differentially expressed in a rostrocaudal pattern in the somites confine the movement of spinal motor axons and neural crest cells to the rostral half of the somitic sclerotome. The expression patterns of transmembrane ephrin-B ligands and interacting EphB receptors suggest that these proteins are likely candidates for coordinating the segmentation of spinal motor axons and neural crest cells. In vitro, ephrin-B1 has indeed been shown to repel axons extending from the rodent neural tube (Wang & Anderson, 1997). In avians, blocking interactions between EphB3 expressed by neural crest cells and ephrin-B1 localized to the caudal half of the somite in vivo resulted in loss of the rostrocaudal patterning of trunk neural crest migration (Krull et al., 1997). The role of ephrin-B1 in patterning spinal motor axon outgrowth in avian embryos was investigated. Ephrin-B1 protein was found to be expressed in the caudal half-sclerotome and in the dermomyotome at the appropriate time to interact with the EphB2 receptor expressed on spinal motor axons. Treatment of avian embryo explants with soluble ephrin-B1, however, did not perturb the segmental outgrowth of spinal motor axons through the rostral half-somite. In contrast, under the same treatment conditions with soluble ephrin-B1, neural crest cells migrated aberrantly through both rostral and caudal somite halves. These results indicate that the interaction between ephrin-B1 and EphB2 is not required for patterning spinal motor axon segmentation. Even though spinal motor axons traverse the same somitic pathway as neural crest cells, different molecular guidance mechanisms appear to influence their movement.

The Ets domain transcription factor Erm distinguishes rat satellite glia from Schwann cells and is regulated in satellite cells by neuregulin signaling.

Distinct glial cell types of the vertebrate peripheral nervous system (PNS) are derived from the neural crest. Here we show that the expression of the Ets domain transcription factor Erm distinguishes satellite glia from Schwann cells beginning early in rat PNS development. In developing dorsal root ganglia (DRG), Erm is present both in presumptive satellite glia and in neurons. In contrast, Erm is not detectable at any developmental stage in Schwann cells in peripheral nerves. In addition, Erm is downregulated in DRG-derived glia adopting Schwann cell traits in culture. Thus, Erm is the first described transcription factor expressed in satellite glia but not in Schwann cells. In culture, the Neuregulin1 (NRG1) isoform GGF2 maintains Erm expression in presumptive satellite cells and reinduces Erm expression in DRG-derived glia but not in Schwann cells from sciatic nerve. These data demonstrate that there are intrinsic differences between these glial subtypes in their response to NRG1 signaling. In neural crest cultures, Erm-positive progenitor cells give rise to two distinct glial subtypes: Erm-positive, Oct-6-negative satellite glia in response to GGF2, and Erm-negative, Oct-6-positive Schwann cells in the presence of serum and the adenylate cyclase activator forskolin. Thus, Erm-positive neural crest-derived progenitor cells and presumptive satellite glia are able to acquire Schwann cell features. Given the in vivo expression of Erm in peripheral ganglia, we suggest that ganglionic Erm-positive cells may be precursors of Schwann cells.

A Tripartite Nuclear Localization Signal in the PDZ-domain Protein L-periaxin

The murine Periaxin gene encodes two PDZ-domain proteins in myelin-forming Schwann cells of the vertebrate peripheral nervous system (Dytrych, L., Sherman, D. L., Gillespie, C. S., and Brophy, P. J. (1998) J. Biol. Chem. 273, 5794-5800). Here we show that L-periaxin is targeted to the nucleus of embryonic Schwann cells. Subsequently, the protein redistributes to the plasma membrane processes of the myelinating Schwann cell where it is believed to function in a signaling complex. In contrast, L-periaxin remains in the nucleus when expressed ectopically in oligodendrocytes, the myelin-forming glia of the central nervous system. The nuclear localization signal (NLS) is basic and tripartite and comprises three signals that act synergistically. Nuclear targeting of L-periaxin is energy-dependent and is inhibited by cell-cell contact. These data show that L-periaxin is a member of a growing family of proteins that can shuttle between the nucleus and cortical signaling/adherence complexes.

Identification of dividing, determined sensory neuron precursors in the mammalian neural crest.

Sensory and autonomic neurons of the vertebrate peripheral nervous system are derived from the neural crest. Here we use the expression of lineage-specific transcription factors as a means to identify neuronal subtypes that develop in rat neural crest cultures grown in a defined medium. Sensory neurons, identified by expression of the POU-domain transcription factor Brn-3.0, develop from dividing precursors that differentiate within 2 days following emigration from the neural tube. Most of these precursors generate sensory neurons even when challenged with BMP2, a factor that induces autonomic neurogenesis in many other cells in the explants. Moreover, BMP2 fails to prevent expression of the sensory-specific basic helix-loop-helix (bHLH) transcription factors neurogenin1, neurogenin2 and neuroD, although it induces expression of the autonomic-specific bHLH factor MASH1 and the paired homeodomain factor Phox2a in other cells. These data suggest that there are mitotically active precursors in the mammalian neural crest that can generate sensory neurons even in the presence of a strong autonomic-inducing cue. Further characterization of the neurons generated from such precursors indicates that, under these culture conditions, they exhibit a proprioceptive and/or mechanosensory, but not nociceptive, phenotype. Such precursors may therefore correspond to a lineally (Frank, E. and Sanes, J. (1991) Development 111, 895-908) and genetically (Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J. (1999) Genes Dev. 13, in press) distinct subset of early-differentiating precursors of large-diameter sensory neurons identified in vivo.

P21 Ras and Phosphatidylinositol-3 Kinase Are Required for Survival of Wild-Type and NF1 Mutant Sensory Neurons

Nerve growth factor (NGF) is a required differentiation and survival factor for sympathetic and a majority of neural crest-derived sensory neurons in the developing vertebrate peripheral nervous system. Although much is known about the function of NGF, the intracellular signaling cascade that it uses continues to be a subject of intense study. p21 ras signaling is considered necessary for sensory neuron survival. How additional intermediates downstream or in parallel may function has not been fully understood yet. Two intracellular signaling cascades, extra cellular regulated kinase (erk) and phosphatidylinositol-3 (PI 3) kinase, transduce NGF signaling in the pheochromocytoma cell line PC12. To elucidate the role these cascades play in survival and differentiation, we used a combination of recombinant adenoviruses and chemical inhibitors to perturb these pathways in sensory neurons from wild-type mice and mice deficient for neurofibromin in which the survival and differentiation pathway is constitutively active. We demonstrate that ras activity is both necessary and sufficient for the survival of embryonic sensory neurons. Downstream of ras, however, the erk cascade is neither required nor sufficient for neuron survival or overall differentiation. Instead, the activity of PI 3 kinase is necessary for the survival of the wild-type and neurofibromin-deficient neurons. Therefore, we conclude that in sensory neurons, NGF acts via a signaling pathway, which includes both ras and PI 3 kinase.

S100alpha and S100beta proteins in human cutaneous sensory corpuscles: effects of nerve and spinal cord injury.

S100 protein in the vertebrate peripheral nervous system consists of homo- or heterodimers of S100alpha and S100beta proteins, the first predominating in neurons and the second in glial cells. Recently, however, occurrence of S100beta protein in neurons has been reported. The expression of S100 protein by Schwann cells, as well as their derivatives in sensory corpuscles, depends on the sensory axon (i.e., the Schwann cell-axon contact). The present study analyzed the distribution of S100alpha and S100beta proteins in human cutaneous sensory corpuscles and the effects of peripheral or central sensory axon severance in the expression of these proteins. Simple or double immunohistochemistry was carried out using a panel of antibodies against S100alpha, S100beta or S100alpha+beta proteins, and the sections were examined by light or laser confocal scanning microscopy. Skin samples were obtained from normal subjects and patients with spinal cord injury, nerve entrapment, and nerve sections plus graft. The lamellar cells of Meissner corpuscles as well as the inner-core lamellae of the Pacinian corpuscles displayed strong immunoreactivity (IR) for all antigens examined, the most intense labeling being obtained for S100beta protein. The pattern of immunostaining was unchanged after spinal cord injury, whereas the number of stained corpuscles as well as the intensity of IR for each antigen decreased in cutaneous sensory corpuscles after nerve injury, both entrapment and section plus graft. No evidence was found of axonal labeling. The present results provide evidence that Schwann-related cells in human cutaneous sensory corpuscles contain both S100alpha and S100beta and that the expression of these proteins is dependent on the functional and structural integrity of sensory fibers.

Cell lineage determination and the control of neuronal identity in the neural crest.

The molecular mechanisms underlying the determination of neuronal identity in the vertebrate peripheral nervous system are only just beginning to come into focus. Many of these mechanisms, such as the involvement of cascades of bHLH transcription factors and lateral inhibition via the Notch-Delta system, appear to have been conserved from Drosophila (Ghysen et al. 1993; Jan and Jan 1993). The way in which these genetic circuits are controlled by instructive growth factors, and the manner in which they lead to expression of a particular neuronal identity, is far from clear. This process is being elucidated by studies of neurogenesis in the peripheral autonomic lineage, which is arguably the best-understood neurogenic lineage in vertebrates. Emerging evidence is beginning to suggest that neuronal diversity within the autonomic and sensory lineages may be generated by related, but distinct, mechanisms. All autonomic progenitors express a common bHLH protein, MASH1, which appears to be induced by members of the BMP2 subfamily secreted by the tissues to which these progenitors migrate. Additional signals may then act on these progenitors in different locations to induce the expression of other transcription factors, which act in conjunction with MASH1 to specify the final phenotypes of the different autonomic neuron subtypes (sympathetic, parasympathetic, and enteric). Although different classes of autonomic neurons develop in very different locations within the body, different classes of sensory neurons are located together in dorsal root ganglia. The finding that distinct but related subtypes of bHLH proteins, the neurogenins, are expressed by different classes of sensory neuron precursors early in development suggests that sensory neuron diversity, in contrast to autonomic neuron diversity, may be pre-specified at or before the time neural crest cells begin their emigration from the neural tube.

Expression Pattern of Collagen IX and Potential Role in the Segmentation of the Peripheral Nervous System

Segmentation of the peripheral nervous system of vertebrates requires guidance cues located in the adjacent somitic mesoderm. Recent experiments suggest that inhibitory molecules in the posterior somite may influence segmentation by restricting the outgrowth of axons and the migration of neural crest cells to the anterior somite. A potential candidate for an inhibitory molecule is collagen IX, a chondroitin sulfate proteoglycan made by sclerotome cells of the somite and by the notochord. Immunohistochemical localization of collagen IX demonstrated that its expression in the posterior sclerotome of the somite correlates with axon outgrowth and neural crest cell migration through the anterior sclerotome.In vitro,sensory neurites on fibronectin, and motor neurites on basal lamina extract, avoid regions which contain substrate-bound collagen IX. This effect can be abolished by chondroitinase treatment, suggesting that the glycosaminoglycan component of the molecule is responsible for this activity. Further, collagen IX elicits a similar avoidance behavior by neural crest cellsin vitro.These data suggest that collagen IX contributes to the segmentation of the peripheral nervous systemin vivo.

Cell death in the Schwann cell lineage and its regulation by neuregulin.

The development of Schwann cells, the myelin-forming glial cells of the vertebrate peripheral nervous system, involves a neonatal phase of proliferation in which cells migrate along and segregate newly formed axons. Withdrawal from the cell cycle, around postnatal days 2-4 in rodents, initiates terminal differentiation to the myelinating state. During this time, Schwann cell number is subject to stringent regulation such that within the first postnatal week, axons and myelinating Schwann cells attain the one-to-one relationship characteristic of the mature nerve. The mechanisms that underly this developmental control remain largely undefined. In this report, we examine the role of apoptosis in the determination of postnatal Schwann cell number. We find that Schwann cells isolated from postnatal day 3 rat sciatic nerve undergo apoptosis in vitro upon serum withdrawal and that Schwann cell death can be prevented by beta forms of neuregulin (NRG-beta) but not by fibroblast growth factor 2 or platelet-derived growth factors AA and BB. This NRG-beta-mediated Schwann cell survival is apparently transduced through an ErbB2/ErbB3 receptor heterodimer. We also provide evidence that postnatal Schwann cells undergo developmentally regulated apoptosis in vivo. Together with other recent findings, these results suggest that Schwann cell apoptosis may play an important role in peripheral nerve development and that Schwann cell survival may be regulated by access to axonally derived NRG.

The postembryonic development of somatostatin immunoreactivity in the central posterior/prepacemaker nucleus of weakly electric fish, Apteronotus leptorhynchus: a double-labelling study

The neuropeptide somatostatin (SS) is widely distributed in both the central and peripheral nervous system of vertebrates. Its widespread distribution is paralleled by a large variety of diverse functions. While embryonic and perinatal development of SS-like immunoreactivity have been well examined, little is known about the postnatal development of this neuropeptide. Since, in teleosts, neurogenesis persists in many brain regions during adulthood, these vertebrates are well suited to investigate this phenomenon. In the present study, we have, therefore, examined the development of somatostatinergic cells born during adulthood in the central posterior/prepacemaker nucleus (CP/PPn) of Apteronotus leptorhynchus, a weakly electric gymnotiform fish. This was achieved by labelling proliferating cells with the thymidine analogue 5-bromo-2′-deoxyuridine (BrdU) and by simultaneous immunocytochemical detection of SS-like immunoreactivity. SS-like immunoreactivity is adopted in a period between 2 days and 3.5 days after birth. While the number of BrdU-labelled cells in the CP/PPn decreases 10 days after birth, the percentage of double-labelled cells among the BrdU-labelled cells remains with 1.0–7.6% in the period between 3.5 days and 100 days after birth rather constant. This percentage matches well the fraction of SS-positive cells in the total population of cells present in the CP/PPn.