Vertebrate Spinal Cord Research Articles

A novel Gli3 enhancer controls the Gli3 spatiotemporal expression pattern through a TALE homeodomain protein binding site.

The zinc finger transcription factor Gli3 is an essential mediator of hedgehog signaling. Gli3 has a dynamic expression pattern during embryonic development. In the neural tube, Gli3 transcripts are patterned along the anteroposterior and dorsoventral axes such that the initial broad expression in the posterior neural tube becomes dorsally restricted as neurogenesis takes place. Little is known about the molecular mechanisms that regulate this dynamic expression. Here, we report on a phylogenetic analysis of the Gli3 locus that uncovered a novel regulatory element, HCNE1. HCNE1 contains a compound Pbx/Meis binding site that binds Pbx and Meis/Prep proteins in vitro and in vivo. We show that HCNE1 recapitulates Gli3 expression in the developing neural tube and that mutations in the Pbx/Meis binding site affect the spatiotemporal control of HCNE1 transcriptional activity. Ectopic expression or loss of function of Pbx and Meis/Prep proteins in the chick and mouse embryo results in aberrant expression of endogenous Gli3 transcripts. We propose a novel role for TALE proteins in establishing the correct spatiotemporal expression pattern of Gli3 in the vertebrate spinal cord, thus implicating TALE transcription factors in early embryonic patterning events controlled by Sonic hedgehog signaling.

Drosophila hedgehogsignaling andengrailed-runtmutual repression direct midline glia to alternative ensheathing and non-ensheathing fates

The Drosophila CNS contains a variety of glia, including highly specialized glia that reside at the CNS midline and functionally resemble the midline floor plate glia of the vertebrate spinal cord. Both insect and vertebrate midline glia play important roles in ensheathing axons that cross the midline and secreting signals that control a variety of developmental processes. The Drosophila midline glia consist of two spatially and functionally distinct populations. The anterior midline glia (AMG) are ensheathing glia that migrate, surround and send processes into the axon commissures. By contrast, the posterior midline glia (PMG) are non-ensheathing glia. Together, the Notch and hedgehog signaling pathways generate AMG and PMG from midline neural precursors. Notch signaling is required for midline glial formation and for transcription of a core set of midline glial-expressed genes. The Hedgehog morphogen is secreted from ectodermal cells adjacent to the CNS midline and directs a subset of midline glia to become PMG. Two transcription factor genes, runt and engrailed, play important roles in AMG and PMG development. The runt gene is expressed in AMG, represses engrailed and maintains AMG gene expression. The engrailed gene is expressed in PMG, represses runt and maintains PMG gene expression. In addition, engrailed can direct midline glia to a PMG-like non-ensheathing fate. Thus, two signaling pathways and runt-engrailed mutual repression initiate and maintain two distinct populations of midline glia that differ functionally in gene expression, glial migration, axon ensheathment, process extension and patterns of apoptosis.

Gradient based axon growth modelling of different cell types with specific growth features in the spinal cord of hatchling Xenopus tadpole

Event Abstract Back to Event Gradient based axon growth modelling of different cell types with specific growth features in the spinal cord of hatchling Xenopus tadpole Abul Kalam Al Azad1*, Roman Borisyuk1, Stephen R Soffe2 and Alan Roberts2 1 University of Plymouth, School of Computing and Mathematics, United Kingdom 2 University of Bristol, School of Biology, United Kingdom It is imperative to understand how simple basic mechanisms can allow primary functioning neuronal circuits to develop. To explore the 'functional connectome', we investigate anatomy and electrophysiology of young hatchling Xenopus tadpole's spinal cord. Our bottom-up approach to modelling of neuronal connectivity is based on developmental process of axon growth - we develop a gradient-based mathematical model for axon growth. It is known that in the developing developing vertebrate spinal cord, axons grow under influence of chemical morphogenes released from the dorsal roof plate ('BMP'), ventral floor plate ('Shh') and hindbrain region ('Wnt'). Distribution of these guidance molecules along the spinal cord set up a gradient field which steer the axons in appropriate locations and thus ensure formation of proper connections. The model of axon growth includes a fixed environment of the governing gradients and seven parameters describing the sensitivity of axon to different guidance molecules. Sensitivity parameters are specific for axons of each cell-type and also they are specific for the direction of axon growth (either to head or tail). A stochastic optimization programming technique is implemented to determine the values of these parameters for each cell-type and each direction of axon growth. The cost function provides a fitting of the model to the experimental measurements of axons and takes into account the projection of the axon to the Dorso-Ventral axis as well as the axon tortuisity. The model successfully generates axons of both commissural and non-commissural neurons which include stimulus receiving sensory neurons, sensory infomation processing interneurons and motorneurons. We model axons of seven types of spinal neurons believed to be involved in swimming and struggling behaviour of tadpole. Each neuron has a different axon growth feature, e.g., commissural neurons grow axons ventrally on the same side of the spinal cord at first and turn longitudinally on the other (contralateral) side of the spinal cord and non-commissural neurons grow their axons on the same (ipsilateral) side of spinal cord. This gradient based axon growth will in fact lead to bilogical reconstruction of the connectome of the tadpole's spinal cord. Keywords: computational neuroscience Conference: 4th INCF Congress of Neuroinformatics, Boston, United States, 4 Sep - 6 Sep, 2011. Presentation Type: Poster Presentation Topic: Computational neuroscience Citation: Azad A, Borisyuk R, Soffe S and Roberts A (2011). Gradient based axon growth modelling of different cell types with specific growth features in the spinal cord of hatchling Xenopus tadpole. Front. Neuroinform. Conference Abstract: 4th INCF Congress of Neuroinformatics. doi: 10.3389/conf.fninf.2011.08.00064 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Oct 2011; Published Online: 19 Oct 2011. * Correspondence: Dr. Abul Kalam Al Azad, University of Plymouth, School of Computing and Mathematics, Plymouth, United Kingdom, abul.azad@plymouth.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Abul Kalam Al Azad Roman Borisyuk Stephen R Soffe Alan Roberts Google Abul Kalam Al Azad Roman Borisyuk Stephen R Soffe Alan Roberts Google Scholar Abul Kalam Al Azad Roman Borisyuk Stephen R Soffe Alan Roberts PubMed Abul Kalam Al Azad Roman Borisyuk Stephen R Soffe Alan Roberts Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Nitric Oxide Synthase Regulates Morphogenesis of Zebrafish Spinal Cord Motoneurons

Nitric oxide (NO) is a signaling molecule that is synthesized in a range of tissues by the NO synthases (NOSs). In the immature nervous system, the neuronal isoform of NOS (NOS1) is often expressed during periods of axon outgrowth and elaboration. However, there is little direct molecular evidence to suggest that NOS1 influences these processes. Here we address the functional role of NOS1 during in vivo zebrafish locomotor circuit development. We show that NOS1 is expressed in a population of interneurons that lie close to nascent motoneurons of the spinal cord. To determine how this protein regulates spinal network assembly, we perturbed NOS1 expression in vivo with antisense morpholino oligonucleotides. This treatment dramatically increased the number of axon collaterals formed by motoneuron axons, an effect mimicked by pharmacological inhibition of the NO/cGMP signaling pathway. In contrast, exogenous elevation of NO/cGMP levels suppressed motor axon branching. These effects were not accompanied by a change in motoneuron number, suggesting that NOS1 does not regulate motoneuron differentiation. Finally we show that perturbation of NO signaling affects the ontogeny of locomotor performance. Our findings provide evidence that NOS1 is a key regulator of motor axon ontogeny in the developing vertebrate spinal cord.

P06. Live-imaging analysis of apoptosis and caspase activation reveals that apoptosis is a facilitator of the neural tube closure

Neural tube closure (NTC) is a fundamental process to construct the brain and the spinal cord in vertebrates. The neural plate develops bilateral neural folds, which in turn come into contact in the midline and fuse together to create the neural tube. Programmed cell death (PCD), especially apoptosis, is widely observed during the process. Several lines of evidence suggested that apoptosis is essential to complete cranial NTC. However, it is still unclear how apoptosis contributes to the completion of cranial NTC. To examine the relationship between dying cells and morphogenetic movement such as neural plate bending, fusion of neural ridge, and epithelial remodeling after the fusion, direct visualization of dying cells during NTC could be effective. We have conducted a live-imaging analysis of apoptosis during cranial NTC with the mouse embryo expressing SCAT3, a fluorescent indicator protein to monitor caspase-3 activation in living cells. In these embryos, caspase activation was observed in dying cells of the pre-fusion neural ridge, fusion point, and the post-fusion midline. Thus, this system allowed us to observe the dynamics of cranial NTC when caspase activation and apoptosis were inhibited. We found that the speed of closure tended to become slow under caspase-inhibited condition, suggesting that caspase activation and apoptosis contribute to the progression of neural tube closure within a limited developmental time window.

Pre‐ and postsynaptic modulation of monosynaptic reflex by GABAA receptors on turtle spinal cord

There is growing evidence that activation of high affinity extrasynaptic GABA(A) receptors in the brain, cerebellum and spinal cord substantia gelatinosa results in a tonic inhibition controlling postsynaptic excitability. The aim of the present study was to determine if GABA(A) receptors mediating tonic inhibition participate in the modulation of monosynaptic reflex (MSR) in the vertebrate spinal cord. Using an in vitro turtle lumbar spinal cord preparation, we show that conditioning stimulation of a dorsal root depressed the test monosynaptic reflex (MSR) at long condition-test intervals. This long duration inhibition is similar to the one seen in mammalian spinal cord and it is dependent on GABA(A) as it was completely blocked by 20 microm picrotoxin (PTX) or bicuculline (BIC) or 1 microm gabazine, simultaneously depressing the dorsal root potential (DRP) without MSR facilitation. Interestingly 100 microm picrotoxin or BIC potentiated the MSR, depressed the DRP, and produced a long lasting motoneurone after-discharge. Furosemide, a selective antagonist of extrasynaptic GABA(A) receptors, affects receptor subtypes with alpha(4/6) subunits, and in a similar way to higher concentrations of PTX or BIC, also potentiated the MSR but did not affect the DRP, suggesting the presence of alpha(4/6) GABA(A) receptors at motoneurones. Our results suggest that (1) the turtle spinal cord has a GABA(A) mediated long duration inhibition similar to presynaptic inhibition observed in mammals, (2) GABA(A) receptors located at the motoneurones and primary afferents might produce tonic inhibition of monosynaptic reflex, and (3) GABA(A) receptors modulate motoneurone excitability reducing the probability of spurious and inappropriate activation.

Cryptic organisation within an apparently irregular rostrocaudal distribution of interneurons in the embryonic zebrafish spinal cord

The molecules and mechanisms involved in patterning the dorsoventral axis of the developing vertebrate spinal cord have been investigated extensively and many are well known. Conversely, knowledge of mechanisms patterning cellular distributions along the rostrocaudal axis is relatively more restricted. Much is known about the rostrocaudal distribution of motoneurons and spinal cord cells derived from neural crest but there is little known about the rostrocaudal patterning of most of the other spinal cord neurons. Here we report data from our analyses of the distribution of dorsal longitudinal ascending (DoLA) interneurons in the developing zebrafish spinal cord. We show that, although apparently distributed irregularly, these cells have cryptic organisation. We present a novel cell-labelling technique that reveals that DoLA interneurons migrate rostrally along the dorsal longitudinal fasciculus of the spinal cord during development. This cell-labelling strategy may be useful for in vivo analysis of factors controlling neuron migration in the central nervous system. Additionally, we show that DoLA interneurons persist in the developing spinal cord for longer than previously reported. These findings illustrate the need to investigate factors and mechanisms that determine “irregular” patterns of cell distribution, particularly in the central nervous system but also in other tissues of developing embryos.

The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline.

Slits and their Roundabout (Robo) receptors mediate repulsive axon guidance at the Drosophila ventral midline and in the vertebrate spinal cord. Slit is cleaved to produce fragments with distinct signaling properties. In a screen for genes involved in Slit-Robo repulsion, we have identified the Adam family metalloprotease Kuzbanian (Kuz). Kuz does not regulate midline repulsion through cleavage of Slit, nor is Slit cleavage essential for repulsion. Instead, Kuz acts in neurons to regulate repulsion and Kuz can cleave the Robo extracellular domain in Drosophila cells. Genetic rescue experiments using an uncleavable form of Robo show that this receptor does not maintain normal repellent activity. Finally, Kuz activity is required for Robo to recruit its downstream signaling partner, Son of sevenless (Sos). These observations support the model that Kuz-directed cleavage is important for Robo receptor activation.

Entrainment ranges of forced phase oscillators

In the vertebrate spinal cord, a neural circuit called the central pattern generator produces the basic locomotory rhythm. Short and long distance intersegmental connections serve to maintain coordination along the length of the body. As a way of examining the influence of such connections, we consider a model of a chain of coupled phase oscillators in which one oscillator receives a periodic forcing stimulus. For a certain range of forcing frequencies, the chain will match the stimulus frequency, a phenomenon called entrainment. Motivated by recent experiments in lampreys, we derive analytical expressions for the range of forcing frequencies that entrain the chain, and how that range depends on the forcing location. For short intersegmental connections, in which an oscillator is connected only to its nearest neighbors, we describe two ways in which entrainment is lost: internally, in which oscillators within the chain no longer oscillate at the same frequency; and externally, in which the the chain no longer has the same frequency as the forcing. By analyzing chains in which every oscillator is connected to every other oscillator (i.e., all-to-all connections), we show that the presence of connections with lengths greater than one do not necessarily change the entrainment ranges based on the nearest-neighbor model. We derive a criterion for the ratio of connection strengths under which the connections of length greater than one do not change the entrainment ranges produced in the nearest-neighbor model, provided entrainment is lost externally. However, when this criterion holds, the range of entrained frequencies is a monotonic function of forcing location, unlike experimental results, in which entrainment ranges are larger near the middle of the chain than at the ends. Numerically, we show that similar non-monotonic entrainment ranges are possible if the ratio criterion does not hold, suggesting that in the lamprey central pattern generator, intersegmental connection strengths are not a simple function of the connection length.

Assaying the Ability of Diffusible Signaling Molecules to Reorient Embryonic Spinal Commissural Axons

Dorsal commissural axons in the vertebrate spinal cord(1) have been an invaluable model system in which to identify axon guidance signals. Here, we describe an in vitro assay, "the reorientation assay", that has been used extensively to study the effect of extrinsic and intrinsic signals on the orientation of commissural axons(2). This assay was developed by numerous people in the laboratories of Jane Dodd, Thomas Jessell and Andrew Lumsden (see acknowledgements for more details) and versions of this assay were used to demonstrate the reorientation activities of key axon guidance molecules, including the BMP chemorepellent in the roof plate(3,4) and the chemoattractive activities of Netrin1(5) and Sonic Hedgehog (Shh)(6) in the floor plate in the spinal cord. Explants comprising 2-3 segments of the dorsal two-thirds of spinal cord are dissected from embryonic day (E) 11 rats and cultured in three dimensional collagen gels(7). E11 dorsal spinal explants contain newly born commissural neurons, which can be identified by their axonal expression of the glycoprotein, Tag1(8). Over the course of 30-40 hours in culture, the commissural axon trajectory is recapitulated in these dorsal explants with a time course similar to that seen in vivo. This axonal trajectory can be challenged by placing either test tissues or a COS cell aggregate expressing a candidate signaling molecule in contact with one of the lateral edges of the dorsal explant. Commissural axons extending in the vicinity of the appended tissue will grow under the influence of both the endogenous roof plate and signals from the ectopic lateral tissue. The degree to which commissural axons are reoriented under these circumstances can be quantified. Using this assay, it is possible both to examine the sufficiency of a particular signal to reorient commissural axons(3,4) as well the necessity for this signal to direct the commissural trajectory(9).

FGF-2 in Astroglial Cells During Vertebrate Spinal Cord Recovery

Fibroblast growth factor-2 is a pleiotrophic cytokine with neurotrophic and gliogenic properties. It is known to regulate CNS injury responses, which include transformation of reactive astrocytes, neurogenesis, and promotion of neurotrophic activities. In the brain, it is localized in astrocytes and discrete neuronal populations. Following both central and peripheral nervous system injury, astrocytes become reactive. These activated cells undergo hypertrophy. A key indicator of astrocyte activation is the increased accumulation of intermediate filaments composed of glial fibrillary acidic protein (GFAP). Following physical insult of brain or spinal cord, reactive astrocytes show increased FGF-2 immunoreactivity. Thus, FGF-2 appears to participate in astrocytic differentiation and proliferation and a good candidate for astrocytic function regulation in healthy, injured, or diseased CNS. To further investigate the cellular mechanisms underlying FGF-2 restorative actions and to analyze the changes within astroglial cells, we studied the localization of GFAP and FGF-2 in adult intact and injured Pleurodeles CNS. Our results show that spinal cord injury triggers a significant increase in FGF-2 immunoreactivity in reactive astrocytes at sites of insult. In addition, these results were time-dependent. Increase in FGF-2 immunoreactivity along the CNS axis, starting 1-week post-injury, was long-lasting extending to 6 weeks. This increase was accompanied by an increase in GFAP immunoreactivity in the same spatial pattern except in SC3 where its level was almost similar to sham-operated animals. Therefore, we suggest that FGF-2 may be involved in cell proliferation and/or astroglial cells differentiation after body spinal cord transection, and could thus play an important role in locomotion recovery.

(RE)DEFINING THE NEURONS THAT CONTROL LOCOMOTION IN VERTEBRATES

![Figure][1] The vertebrate spinal cord generates oscillations that ultimately produce the alternating left–right body movements that characterize running, walking and swimming. It has long been hypothesized that the circuitry that produces these spinal cord rhythms resides in the spinal

Optogenetic dissection of a behavioural module in the vertebrate spinal cord

Locomotion relies on neural networks called central pattern generators (CPGs) that generate periodic motor commands for rhythmic movements1. We have identified a spinal input to the CPG that drives spontaneous locomotion using a combination of intersectional gene expression and optogenetics2 in zebrafish larvae. The photo-stimulation of one specific cell type was sufficient to induce a symmetrical tail beating sequence that mimics spontaneous slow forward swimming. This neuron is the Kolmer-Agduhr (KA) cell3, which extends cilia into the central cerebrospinal fluid containing canal of the spinal cord and has an ipsilateral ascending axon that terminates in a series of consecutive segments4. Genetically silencing KA cells reduced the frequency of spontaneous free swimming, indicating that KA cell activity provides necessary tone for spontaneous forward swimming. KA cells have been known for over 75 years, but their function has been mysterious. Our results reveal that during early development in low vertebrates these cells provide a positive drive to the spinal CPG for spontaneous locomotion.

Genetic dissection of dopaminergic and noradrenergic contributions to catecholaminergic tracts in early larval zebrafish.

The catecholamines dopamine and noradrenaline provide some of the major neuromodulatory systems with far-ranging projections in the brain and spinal cord of vertebrates. However, development of these complex systems is only partially understood. Zebrafish provide an excellent model for genetic analysis of neuronal specification and axonal projections in vertebrates. Here, we analyze the ontogeny of the catecholaminergic projections in zebrafish embryos and larvae up to the fifth day of development and establish the basic scaffold of catecholaminergic connectivity. The earliest dopaminergic diencephalospinal projections do not navigate along the zebrafish primary neuron axonal scaffold but establish their own tracts at defined ventrolateral positions. By using genetic tools, we study quantitative and qualitative contributions of noradrenergic and defined dopaminergic groups to the catecholaminergic scaffold. Suppression of Tfap2a activity allows us to eliminate noradrenergic contributions, and depletion of Otp activity deletes mammalian A11-like Otp-dependent ventral diencephalic dopaminergic groups. This analysis reveals a predominant contribution of Otp-dependent dopaminergic neurons to diencephalospinal as well as hypothalamic catecholaminergic tracts. In contrast, noradrenergic projections make only a minor contribution to hindbrain and spinal catecholaminergic tracts. Furthermore, we can demonstrate that, in zebrafish larvae, ascending catecholaminergic projections to the telencephalon are generated exclusively by Otp-dependent diencephalic dopaminergic neurons as well as by hindbrain noradrenergic groups. Our data reveal the Otp-dependent A11-type dopaminergic neurons as the by far most prominent dopaminergic system in larval zebrafish. These findings are consistent with a hypothesis that Otp-dependent dopaminergic neurons establish the major modulatory system for somatomotor and somatosensory circuits in larval fish. J. Comp. Neurol. 518:439–458, 2010. © 2009 Wiley-Liss, Inc.

Modulation of Intrinsic Spiking in Spinal Cord Neurons

The vertebrate spinal cord is equipped with a number of neuronal networks that underlie repetitive patterns of behavior as locomotion. Activity in such networks is mediated not only by intrinsic cellular properties but also by synaptic coupling. In this study, we focused on the modulation of the intrinsic activity by 5-hydroxytryptamine (5-HT, serotonin) and the cholinergic agonist muscarine in spinal cord cultures (embryonic age 14 rats). We investigated theses cultures (slices and dissociated cells) at the network level using multielectrode arrays (MEAs) and at the cellular level using whole cell patch clamp. All cultures showed bursting network activity and intrinsic activity when gamma-aminobutyric acid, glycine, and glutamate transmission was blocked. Using MEAs, we observed an increase of the intrinsic activity in the ventral part of the slices with 5-HT and muscarine. In single-cell recordings we found that 43 and 35% of the cells that were silent in the absence of fast synaptic activity were transformed into intrinsically spiking cells by 5-HT and muscarine, respectively. We tested the hypothesis that these neuromodulators act via modulation of the persistent sodium currents (I(NaP)) in these neurons. We found that 5-HT increased threefold the amplitude of I(NaP), specifically in the nonintrinsically spiking cells, and thus switched these cells into intrinsically spiking cells via activation of 5-HT(2) receptor and the phospholipase C pathway. In contrast, the effect of muscarine on nonintrinsically spiking neurons seems to be independent of I(NaP). We conclude from these findings that serotoninergic and cholinergic modulation can turn silent into spontaneously spiking neurons and thus initiate new sources of activity for rhythm generation in spinal networks.

13-P081 Distinct dynamics of Sonic Hedgehog signaling are required to specify floor plate and ventral neuronal identities in the vertebrate spinal cord

13-P081 Distinct dynamics of Sonic Hedgehog signaling are required to specify floor plate and ventral neuronal identities in the vertebrate spinal cord

Deal Breaker: Semaphorin and Specificity in the Spinal Stretch Reflex Circuit

Stretch reflex circuits are a prime example of wiring specificity in the vertebrate spinal cord. Homonymous sensory afferents and motoneurons typically form monosynaptic connections, while neurons innervating antagonistic or unrelated muscles do not. Pecho-Vrieseling et al. now show that the semaphorin Sema3E and its receptor Plexin-D1 prevent monosynaptic connectivity in the cutaneous maximus muscle stretch reflex circuit.

Opposing Aminergic Modulation of Distinct Spinal Locomotor Circuits and Their Functional Coupling during Amphibian Metamorphosis

The biogenic amines serotonin (5-HT) and noradrenaline (NA) are well known modulators of central pattern-generating networks responsible for vertebrate locomotion. Here we have explored monoaminergic modulation of the spinal circuits that generate two distinct modes of locomotion in the metamorphosing frog Xenopus laevis. At metamorphic climax when propulsion is achieved by undulatory larval tail movements and/or by kicking of the newly developed adult hindlimbs, the underlying motor networks remain spontaneously active in vitro, producing either separate fast axial and slow appendicular rhythms or a single combined rhythm that drives coordinated tail-based and limb-based swimming in vivo. In isolated spinal cords already expressing distinct axial and limb rhythms, bath-applied 5-HT induced coupled network activity through an opposite slowing of axial rhythmicity (by increasing motoneuron burst and cycle durations) and an acceleration of limb rhythmicity (by decreasing burst and cycle durations). In contrast, in preparations spontaneously expressing coordinated fictive locomotion, exogenous NA caused a dissociation of spinal activity into separate faster axial and slower appendicular rhythms by decreasing and increasing burst and cycle durations, respectively. Moreover, in preparations from premetamorphic and postmetamorphic animals that express exclusively axial-based or limb-based locomotion, 5-HT and NA modified the developmentally independent rhythms in a similar manner to the amines' opposing effects on the coexisting circuits at metamorphic climax. Thus, by exerting differential modulatory actions on one network that are opposite to their influences on a second adjacent circuit, these two amines are able to precisely regulate the functional relationship between different rhythmogenic networks in a developing vertebrate's spinal cord.

FGF-2 in Astroglial Cells during Vertebrate Spinal Cord Recovery

Event Abstract Back to Event FGF-2 in Astroglial Cells during Vertebrate Spinal Cord Recovery Gehan Fahmy1 and Marie Moftah1* 1 Alexandria University, Zoology Department, Faculty of Science, Egypt FGF-2 is a pleiotrophic cytokine with neurotrophic and gliogenic properties both in vivo and in vitro. In the brain, it is localized in astrocytes and discrete neuronal populations. FGF-2 is known to regulate CNS injury responses, which include transformation of reactive astrocytes, scar formation, neurogenesis, and promotion of neurotrophic activities. Astrocytes become reactive following both central and peripheral nervous system injury. These activated cells undergo hypertrophy. A key indicator of astrocyte activation is the increased accumulation of intermediate filaments composed of glial fibrillary acidic protein (GFAP). Following a physical insult to brain or spinal cord, reactive astrocytes near the damage site show increased FGF-2 immunoreactivity. Thus, FGF-2 appears to participate in astrocytic differentiation and proliferation and a good candidate for astrocytic function regulation in healthy, injured, or diseased CNS. To further investigate the cellular mechanisms underlying FGF-2 restorative actions and to analyze, in more details, the changes within astroglial cells, we studied the localization of GFAP and FGF-2 in adult intact and injured Pleurodeles CNS. Our results show that spinal cord injury triggers a significant increase in FGF-2 immunoreactivity in reactive astrocytes at sites of insult. In addition, these results were time-dependent. Increase in FGF-2 immunoreactivity along the CNS axis, starting 1-week post-injury, was long-lasting extending to 6 weeks. This increase was accompanied by an increase in GFAP immunoreactivity in the same spatial pattern except in SC3 where its level was almost similar to sham-operated animals. Therefore, we suggest that FGF2 may be involved in cell proliferation and/or astroglial cells differentiation after body spinal cord transection in salamander, and could thus play an important role in locomotion recovery after spinal lesion.Acknowledgments: Part of the experiments were performed in the physiopathology of neuronal networks laboratory, INSERM U862, Equipe NAGY, Neurocentre Magendie, 146 rue Leo Saignat, 33077 Bordeaux Cedex, France. Keywords: Fibroblast growth factor-2 (FGF-2), Nerve Regeneration, Pleurodele waltlii Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Topic: CNS Diseases Citation: Fahmy G and Moftah M (2009). FGF-2 in Astroglial Cells during Vertebrate Spinal Cord Recovery. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.151 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Nov 2009; Published Online: 25 Nov 2009. * Correspondence: Marie Moftah, Alexandria University, Zoology Department, Faculty of Science, Alexandria, Egypt, marie.moftah@alexu.edu.eg Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gehan Fahmy Marie Moftah Google Gehan Fahmy Marie Moftah Google Scholar Gehan Fahmy Marie Moftah PubMed Gehan Fahmy Marie Moftah Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Zebrafish V2 cells develop into excitatory CiD and Notch signalling dependent inhibitory VeLD interneurons

The vertebrate spinal cord contains distinct classes of cells that form at precise dorsal–ventral locations and express specific combinations of transcription factors. In amniotes, V2 cells develop in the ventral spinal cord, just dorsal to motoneurons. All V2 cells develop from the same progenitor domain and hence are initially molecularly identical. However, as they start to become post-mitotic and differentiate they subdivide into two intermingled molecularly-distinct subpopulations of cells, V2a and V2b cells. Here we show that the molecular identities of V2a and V2b cells are conserved between zebrafish and amniotes. In zebrafish, these two cell types both develop into interneurons with very similar morphologies, but while V2a cells become excitatory Circumferential Descending (CiD) interneurons, V2b cells become inhibitory Ventral Lateral Descending (VeLD) interneurons. In addition, we demonstrate that Notch signalling is required for V2 cells to develop into V2b cells. In the absence of Notch signalling, all V2b cells develop as V2a cells.