Vertebrate Central Nervous System Research Articles

Notch-mediated re-specification of neuronal identity during central nervous system development

Neuronal identity has long been thought of as immutable, so that once a cell acquires a specific fate, it is maintained for life.1 Studies using the overexpression of potent transcription factors to experimentally reprogram neuronal fate in the mouse neocortex2,3 and retina4,5 have challenged this notion by revealing that post-mitotic neurons can switch their identity. Whether fate reprogramming is part of normal development in the central nervous system (CNS) is unclear. While there are some reports of physiological cell fate reprogramming in invertebrates,6,7 and in the vertebrate peripheral nervous system,8 endogenous fate reprogramming in the vertebrate CNS has not been documented. Here, we demonstrate spontaneous fate re-specification in an interneuron lineage in the zebrafish retina. We show that the visual system homeobox 1 (vsx1)-expressing lineage, which has been associated exclusively with excitatory bipolar cell (BC) interneurons,9-12 also generates inhibitory amacrine cells (ACs). We identify a role for Notch signaling in conferring plasticity to nascent vsx1 BCs, allowing suitable transcription factor programs to re-specify them to an AC fate. Overstimulating Notch signaling enhances this physiological phenotype so that both daughters of a vsx1 progenitor differentiate into ACs and partially differentiated vsx1 BCs can be converted into ACs. Furthermore, this physiological re-specification can be mimicked to allow experimental induction of an entirely distinct fate, that of retinal projection neurons, from the vsx1 lineage. Our observations reveal unanticipated plasticity of cell fate during retinal development.

Chromatin remodeling in oligodendrogenesis.

Oligodendrocytes are one type of glial cells responsible for myelination and providing trophic support for axons in the central nervous system of vertebrates. Thanks to myelin, the speed of electrical-signal conduction increases several hundred-fold because myelin serves as a kind of electrical insulator of nerve f ibers and allows for quick saltatory conduction of action potentials through Ranvier nodes, which are devoid of myelin. Given that different parts of the central nervous system are myelinated at different stages of development and most regions contain both myelinated and unmyelinated axons, it is obvious that very precise mechanisms must exist to control the myelination of individual axons. As they go through the stages of specif ication and differentiation – from multipotent neuronal cells in the ventricular zone of the neural tube to mature myelinating oligodendrocytes as well as during migration along blood vessels to their destination – cells undergo dramatic changes in the pattern of gene expression. These changes require precisely spatially and temporally coordinated interactions of various transcription factors and epigenetic events that determine the regulatory landscape of chromatin. Chromatin remodeling substantially affects transcriptional activity of genes. The main component of chromatin is the nucleosome, which, in addition to the structural function, performs a regulatory one and serves as a general repressor of genes. Changes in the type, position, and local density of nucleosomes require the action of specialized ATPdependent chromatin-remodeling complexes, which use the energy of ATP hydrolysis for their activity. Mutations in the genes encoding proteins of the remodeling complexes are often accompanied by serious disorders at early stages of embryogenesis and are frequently identif ied in various cancers. According to the domain arrangement of the ATP-hydrolyzing subunit, most of the identif ied ATP-dependent chromatin-remodeling complexes are classif ied into four subfamilies: SWI/SNF, CHD, INO80/SWR, and ISWI. In this review, we discuss the roles of these subunits of the different subfamilies at different stages of oligodendrogenesis

The killifish visual system as an in vivo model to study brain aging and rejuvenation

Worldwide, people are getting older, and this prolonged lifespan unfortunately also results in an increased prevalence of age-related neurodegenerative diseases, contributing to a diminished life quality of elderly. Age-associated neuropathies typically include diseases leading to dementia (Alzheimer’s and Parkinson’s disease), as well as eye diseases such as glaucoma and age-related macular degeneration. Despite many research attempts aiming to unravel aging processes and their involvement in neurodegeneration and functional decline, achieving healthy brain aging remains a challenge. The African turquoise killifish (Nothobranchius furzeri) is the shortest-lived reported vertebrate that can be bred in captivity and displays many of the aging hallmarks that have been described for human aging, which makes it a very promising biogerontology model. As vision decline is an important hallmark of aging as well as a manifestation of many neurodegenerative diseases, we performed a comprehensive characterization of this fish’s aging visual system. Our work reveals several aging hallmarks in the killifish retina and brain that eventually result in a diminished visual performance. Moreover, we found evidence for the occurrence of neurodegenerative events in the old killifish retina. Altogether, we introduce the visual system of the fast-aging killifish as a valuable model to understand the cellular and molecular mechanisms underlying aging in the vertebrate central nervous system. These findings put forward the killifish for target validation as well as drug discovery for rejuvenating or neuroprotective therapies ensuring healthy aging.

Met is required for oligodendrocyte progenitor cell migration in Danio rerio.

During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.

Vibrational spectroscopy and phonon‐related properties of monoclinic GABA, a non‐proteinogenic inhibitory neurotransmitter amino acid

AbstractThe γ‐aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in vertebrate central nervous systems. Taking full account of the measured X‐ray diffractogram of its stable monoclinic polymorph, we have performed density functional theory (DFT) calculations to analyze/understand its infrared and Raman spectra considering its monoclinic polymorph, an isolated stabilized (120) plane, and a single GABA molecule. Besides, phonon dispersion/density of states, heat capacity, Debye temperature, and entropy/enthalpy/free energies were also obtained for the GABA monoclinic crystal. Vibrational signatures due to the GABA (120) planes are pointed out for the first time for several wavenumbers. The results obtained for the GABA monoclinic polymorph reinforce the need of dispersion‐corrected solid‐state calculations to describe the vibrational properties of molecular crystals instead of considering a single isolated molecule picture, even for wavenumbers larger than those usually associated with lattice modes.

Glial Cells Promote Myelin Formation and Elimination.

Building a functional nervous system requires the coordinated actions of many glial cells. In the vertebrate central nervous system (CNS), oligodendrocytes myelinate neuronal axons to increase conduction velocity and provide trophic support. Myelination can be modified by local signaling at the axon-myelin interface, potentially adapting sheaths to support the metabolic needs and physiology of individual neurons. However, neurons and oligodendrocytes are not wholly responsible for crafting the myelination patterns seen in vivo. Other cell types of the CNS, including microglia and astrocytes, modify myelination. In this review, I cover the contributions of non-neuronal, non-oligodendroglial cells to the formation, maintenance, and pruning of myelin sheaths. I address ways that these cell types interact with the oligodendrocyte lineage throughout development to modify myelination. Additionally, I discuss mechanisms by which these cells may indirectly tune myelination by regulating neuronal activity. Understanding how glial-glial interactions regulate myelination is essential for understanding how the brain functions as a whole and for developing strategies to repair myelin in disease.

Ilex kudingcha C.J. Tseng Mitigates Phenotypic Characteristics of Human Autism Spectrum Disorders in a Drosophila Melanogaster Rugose Mutant.

Autism spectrum disorders (ASD) have heterogeneous etiologies involving dysfunction of central nervous systems, for which no effective pan-specific treatments are available. Ilex kudingcha (IK) C.J. Tseng is a nootropic botanical used in Asia for neuroprotection and improvement of cognition. This study establishes that a chemically characterized extract from IK (IKE) mitigates behavioral traits in the Drosophila melanogaster rugose mutant, whose traits resemble human ASD, and examines possible mechanisms. IKE treatment significantly ameliorated deficits in social interaction, short-term memory, and locomotor activity in Drosophila rugose, and significantly increased synaptic bouton number of size more than 2 μm2 in the neuromuscular junctions (NMJs) of Drosophila rugose. To clarify mechanism(s) of IKE action, methylphenidate (MPH), a dopamine transporter inhibitor, was included as a reference drug in the behavioral assays: MPH significantly improved social interaction and short-term memory deficit in Drosophila rugose; administration of the dopamine D1 receptor antagonist SCH23390 and dopamine D2 receptor antagonist sulpiride reversed the ameliorative effects of both MPH and IKE on the social interaction deficits of Drosophila rugose. To extend analysis of IKE treatment to the vertebrate central nervous system, ASD-associated gene expression in mouse hippocampus was studied by RNA-seq: IKE treatment altered the expression of genes coding phosphoinositide 3-kinases/protein kinase B (PI3K-Akt), proteins in glutamatergic, dopaminergic, serotonergic, and GABAergic synapses, cAMP response element-binding protein (CREB), and RNA transporter proteins. These results provide a foundation for further analysis of IKE as a candidate for treatment of some forms of ASD.

Effect of Prenatal Topiramate Administration on Early Postnatal Expression of GFAP in Radial Glial Cells in Albino Rat Cerebellum and Spinal Cord

Background: Topiramate is known as a modern drug approved for the treatment of patients with partial seizures. Radial glial cells are bipolar-shaped cells in the developing central nervous system of vertebrates. It can differentiate into other neurons and astrocytes. GFAP, Glial fibrillary acidic protein, is a glial intermediate filament protein that is known as the most comprehensive marker for astroglial cells including the radial glia Aim of the work: There are few reports on topiramate administration during pregnancy. Therefore, this drug was chosen to investigate its effects, if any, especially the expression of GFAP in radial glia in the pups’ cerebellum and spinal cord. Material and Methods: Male and female rats were coupled in one cage for mating. On the next morning, mating was approved by the presence of sperms in the female vaginal swab, it was considered as Gestation Day zero:0. Twelve female pregnant rats were divided equally into two groups; control and topiramate treated. Topiramate drug was given to the treated group via orogastric tube from GD zero (0) till the time of delivery in a dose of 100mg/kg the control rats were administered tap water by orogastric tube. At the end of the experiment, the newly born pups (PN1) were weighed, anesthetized with Ketamine (60 mg/kg i.p.). The cerebellum and spinal cord were dissected and weighted. The specimens were fixed in Bouin’s solution then processed for preparation of H& E and GFAP immunostained sections. Results:In H& E-stained sections, the cerebellum in the control group was formed of subsequent layers, purkinje cells were arranged in one row, rounded or fusiform shape. GFAP positive Immunostained radial fibers (Bregman glia) were detected in granular and purkinje cell layers. The treated group showed that cells were disorganized and degenerated with focal areas of neuronal loss. Weak GFAP reaction was observed in Bregman glia in granular, purkinje and white matter cell layers. The lumbosacral segment of the spinal cord ventral horn showed large multipolar motor neurons with vesicular nucleus (“owl-eye” appearance), dendrites and axons were obvious. Glial cells with deeply stained nuclei were noticed. In the treated group, neurons appeared degenerated, vacuolated cytoplasm and pyknotic nuclei with focal areas of cellular loss. GFAP immunostained section in the control group showed an intense reaction in the radial fibers of the glia of the ventral funiculus, in contrast to the treated group which showed a faint reaction in both ventral funiculus and horn. Conclusion: it could be concluded that daily regular administration of topiramate during a childbearing period in females may result in a neurotoxic effect in the cerebellum and spinal cord. So, the administration of this drug should be under strict medical observation.

Müller glia-myeloid cell crosstalk accelerates optic nerve regeneration in the adult zebrafish.

Neurodegenerative disorders, characterized by progressive neuronal loss, eventually lead to functional impairment in the adult mammalian central nervous system (CNS). Importantly, these deteriorations are irreversible, due to the very limited regenerative potential of these CNS neurons. Stimulating and redirecting neuroinflammation was recently put forward as an important approach to induce axonal regeneration, but it remains elusive how inflammatory processes and CNS repair are intertwined. To gain more insight into these interactions, we investigated how immunomodulation affects the regenerative outcome after optic nerve crush (ONC) in the spontaneously regenerating zebrafish. First, inducing intraocular inflammation using zymosan resulted in an acute inflammatory response, characterized by an increased infiltration and proliferation of innate blood-borne immune cells, reactivation of Müller glia, and altered retinal cytokine expression. Strikingly, inflammatory stimulation also accelerated axonal regrowth after optic nerve injury. Second, we demonstrated that acute depletion of both microglia and macrophages in the retina, using pharmacological treatments with both the CSF1R inhibitor PLX3397 and clodronate liposomes, compromised optic nerve regeneration. Moreover, we observed that csf1ra/b double mutant fish, lacking microglia in both retina and brain, displayed accelerated RGC axonal regrowth after ONC, which was accompanied with unusual Müller glia proliferative gliosis. Altogether, our results highlight the importance of altered glial cell interactions in the axonal regeneration process after ONC in adult zebrafish. Unraveling the relative contribution of the different cell types, as well as the signaling pathways involved, may pinpoint new targets to stimulate repair in the vertebrate CNS.

Lipid Signaling through G Proteins.

N-Acylethanolamine (NAE) signaling has received considerable attention in vertebrates as part of the endocannabinoid signaling system, where anandamide acts as a ligand for G protein-coupled cannabinoid receptors. Recent studies indicate that G proteins also are required for some types of NAE signaling in plants. The genetic ablation of the Gβγ dimer or loss of the full set of extra-large G proteins strongly attenuated NAE-induced chloroplast responses in seedlings. Intriguing parallels and distinct differences have emerged between plants and animals in NAE signaling, despite the conserved use of these lipid mediators to modulate cellular processes. Here we compare similarities and differences and identify open questions in a fundamental lipid signaling pathway in eukaryotes with components that are both conserved and diverged in plants.

Каналоблокаторы ионотропных рецепторов глутамата

Glutamatergic transmission is responsible for the majority of excitatory synaptic processes in the central nervous system of vertebrates. Glutamatergic synapses are involved in the vast majority of physiological and pathological processes, and their modulation has a direct impact on almost all brain functions. It is not surprising that the development and research of drugs that can affect the glutamatergic synapses has been and is one of the priorities of neuropharmacology. To give even a brief overview of this complex problem is not a task that can be solved in a single article, so the review presents data on only one of the topics, namely, the ligands, which directly block the ion pores of glutamate-activated channels.

Structural and Functional Plasticity in the Regenerating Olfactory System of the Migratory Locust.

Regeneration after injury is accompanied by transient and lasting changes in the neuroarchitecture of the nervous system and, thus, a form of structural plasticity. In this review, we introduce the olfactory pathway of a particular insect as a convenient model to visualize neural regeneration at an anatomical level and study functional recovery at an electrophysiological level. The olfactory pathway of the locust (Locusta migratoria) is characterized by a multiglomerular innervation of the antennal lobe by olfactory receptor neurons. These olfactory afferents were axotomized by crushing the base of the antenna. The resulting degeneration and regeneration in the antennal lobe could be quantified by size measurements, dye labeling, and immunofluorescence staining of cell surface proteins implicated in axonal guidance during development. Within 3 days post lesion, the antennal lobe volume was reduced by 30% and from then onward regained size back to normal by 2 weeks post injury. The majority of regenerating olfactory receptor axons reinnervated the glomeruli of the antennal lobe. A few regenerating axons project erroneously into the mushroom body on a pathway that is normally chosen by second-order projection neurons. Based on intracellular responses of antennal lobe output neurons to odor stimulation, regenerated fibers establish functional synapses again. Following complete absence after nerve crush, responses to odor stimuli return to control level within 10–14 days. On average, regeneration of afferents, and re-established synaptic connections appear faster in younger fifth instar nymphs than in adults. The initial degeneration of olfactory receptor axons has a trans-synaptic effect on a second order brain center, leading to a transient size reduction of the mushroom body calyx. Odor-evoked oscillating field potentials, absent after nerve crush, were restored in the calyx, indicative of regenerative processes in the network architecture. We conclude that axonal regeneration in the locust olfactory system appears to be possible, precise, and fast, opening an avenue for future mechanistic studies. As a perspective of biomedical importance, the current evidence for nitric oxide/cGMP signaling as positive regulator of axon regeneration in connectives of the ventral nerve cord is considered in light of particular regeneration studies in vertebrate central nervous systems.

Fate restrictions in embryonic neural progenitors.

The vertebrate central nervous system (CNS) is a fantastically complex organ composed of dozens of cell types within the neural and glial lineages. Its organization is laid down during development, through the localized and sequential production of subsets of neurons with specific identities. The principles and mechanisms that underlie the timely production of adequate classes of cells are only partially understood. Recent advances in molecular profiling describe the developmental trajectories leading to this amazing cellular diversity and provide us with cell atlases of an unprecedented level of precision. Yet, some long-standing questions pertaining to lineage relationships between neural progenitor cells and their differentiated progeny remain unanswered. Here, we discuss questions related to proliferation potential, timing of fate choices and restriction of neuronal output potential of individual CNS progenitors through the lens of lineage relationship. Unlocking methodological barriers will be essential to accurately describe CNS development at a cellular resolution.

Emerging orthobunyaviruses associated with CNS disease.

The Orthobunyavirus genus comprises a wide range of arthropod-borne viruses which are prevalent worldwide and commonly associated with central nervous system (CNS) disease in humans and other vertebrates. Several orthobunyaviruses have recently emerged and increasingly more will likely do so in the future. Despite this large number, an overview of these viruses is currently lacking, making it challenging to determine importance from a One Health perspective. Causality is a key feature of determining importance, yet classical tools are unfit to evaluate the causality of orthobunyaviral CNS disease. Therefore, we aimed to provide an overview of orthobunyaviral CNS disease in vertebrates and objectify the causality strength of each virus. In total, we identified 27 orthobunyaviruses described in literature to be associated with CNS disease. Ten were associated with disease in multiple host species of which seven included humans. Seven viruses were associated with both congenital and postnatal CNS disease. CNS disease-associated orthobunyaviruses were spread across all known Orthobunyavirus serogroups by phylogenetic analyses. Taken together, these results indicate that orthobunyaviruses may have a common tendency to infect the CNS of vertebrates. Next, we developed six tailor-made causality indicators and evaluated the causality strength of each of the identified orthobunyaviruses. Nine viruses had a ‘strong’ causality score and were deemed causal. Eight had a ‘moderate’ and ten a ‘weak’ causality score. Notably, there was a lack of case-control studies, which was only available for one virus. We, therefore, stress the importance of proper case-control studies as a fundamental aspect of proving causality. This comprehensible overview can be used to identify orthobunyaviruses which may be considered causal, reveal research gaps for viruses with moderate to low causality scores, and provide a framework to evaluate the causality of orthobunyaviruses that may newly emerge in the future.

Cadherins regulate nuclear topography and function of developing ocular motor circuitry

In the vertebrate central nervous system, groups of functionally related neurons, including cranial motor neurons of the brainstem, are frequently organised as nuclei. The molecular mechanisms governing the emergence of nuclear topography and circuit function are poorly understood. Here we investigate the role of cadherin-mediated adhesion in the development of zebrafish ocular motor (sub)nuclei. We find that developing ocular motor (sub)nuclei differentially express classical cadherins. Perturbing cadherin function in these neurons results in distinct defects in neuronal positioning, including scattering of dorsal cells and defective contralateral migration of ventral subnuclei. In addition, we show that cadherin-mediated interactions between adjacent subnuclei are critical for subnucleus position. We also find that disrupting cadherin adhesivity in dorsal oculomotor neurons impairs the larval optokinetic reflex, suggesting that neuronal clustering is important for co-ordinating circuit function. Our findings reveal that cadherins regulate distinct aspects of cranial motor neuron positioning and establish subnuclear topography and motor function.

Complex crosstalk of Notch and Hedgehog signalling during the development of the central nervous system.

The development of the vertebrate central nervous system (CNS) is tightly regulated by many highly conserved cell signalling pathways. These pathways ensure that differentiation and migration events occur in a specific and spatiotemporally restricted manner. Two of these pathways, Notch and Hedgehog (Hh) signalling, have been shown to form a complex web of interaction throughout different stages of CNS development. Strikingly, some processes employ Notch signalling to regulate Hh response, while others utilise Hh signalling to modulate Notch response. Notch signalling functions upstream of Hh response through controlling the trafficking of integral pathway components as well as through modulating protein levels and transcription of downstream transcriptional factors. In contrast, Hh signalling regulates Notch response by either indirectly controlling expression of key Notch ligands and regulatory proteins or directly through transcriptional control of canonical Notch target genes. Here, we review these interactions and demonstrate the level of interconnectivity between the pathways, highlighting context-dependent modes of crosstalk. Since many other developmental signalling pathways are active in these tissues, it is likely that the interplay between Notch and Hh signalling is not only an example of signalling crosstalk but also functions as a component of a wider, multi-pathway signalling network.

Subpopulations of Projection Neurons in the Olfactory Bulb.

Generation of neuronal diversity is a biological strategy widely used in the brain to process complex information. The olfactory bulb is the first relay station of olfactory information in the vertebrate central nervous system. In the olfactory bulb, axons of the olfactory sensory neurons form synapses with dendrites of projection neurons that transmit the olfactory information to the olfactory cortex. Historically, the olfactory bulb projection neurons have been classified into two populations, mitral cells and tufted cells. The somata of these cells are distinctly segregated within the layers of the olfactory bulb; the mitral cells are located in the mitral cell layer while the tufted cells are found in the external plexiform layer. Although mitral and tufted cells share many morphological, biophysical, and molecular characteristics, they differ in soma size, projection patterns of their dendrites and axons, and odor responses. In addition, tufted cells are further subclassified based on the relative depth of their somata location in the external plexiform layer. Evidence suggests that different types of tufted cells have distinct cellular properties and play different roles in olfactory information processing. Therefore, mitral and different types of tufted cells are considered as starting points for parallel pathways of olfactory information processing in the brain. Moreover, recent studies suggest that mitral cells also consist of heterogeneous subpopulations with different cellular properties despite the fact that the mitral cell layer is a single-cell layer. In this review, we first compare the morphology of projection neurons in the olfactory bulb of different vertebrate species. Next, we explore the similarities and differences among subpopulations of projection neurons in the rodent olfactory bulb. We also discuss the timing of neurogenesis as a factor for the generation of projection neuron heterogeneity in the olfactory bulb. Knowledge about the subpopulations of olfactory bulb projection neurons will contribute to a better understanding of the complex olfactory information processing in higher brain regions.

Mechanisms of vertebrate neural plate internalization.

The internalization of multi-cellular tissues is a key morphogenetic process during animal development and organ formation. A good example of this is the initial stages of vertebrate central nervous system formation whereby a transient embryonic structure called the neural plate is able to undergo collective cell rearrangements within the dorsal midline. Despite the fact that defects in neural plate midline internalization may result in a series of severe clinical conditions, such as spina bifida and anencephaly, the biochemical and biomechanical details of this process remain only partially characterized. Here we review the main cellular and molecular mechanisms underlying midline cell and tissue internalization during vertebrate neural tube formation. We discuss the contribution of collective cell mechanisms including convergence and extension, as well as apical constriction facilitating midline neural plate shaping. Furthermore, we summarize recent studies that shed light on how the interplay of signaling pathways and cell biomechanics modulate neural plate internalization. In addition, we discuss how adhesion-dependent cell-cell contact appears to be a critical component during midline cell convergence and surface cell contraction via cell-cell mechanical coupling. We envision that more detailed high-resolution quantitative data at both cell and tissue levels will be required to properly model the mechanisms of vertebrate neural plate internalization with the hope of preventing human neural tube defects.

Comparative gene expression profiling between optic nerve and spinal cord injury in Xenopus laevis reveals a core set of genes inherent in successful regeneration of vertebrate central nervous system axons

BackgroundThe South African claw-toed frog, Xenopus laevis, is uniquely suited for studying differences between regenerative and non-regenerative responses to CNS injury within the same organism, because some CNS neurons (e.g., retinal ganglion cells after optic nerve crush (ONC)) regenerate axons throughout life, whereas others (e.g., hindbrain neurons after spinal cord injury (SCI)) lose this capacity as tadpoles metamorphose into frogs. Tissues from these CNS regions (frog ONC eye, tadpole SCI hindbrain, frog SCI hindbrain) were used in a three-way RNA-seq study of axotomized CNS axons to identify potential core gene expression programs for successful CNS axon regeneration.ResultsDespite tissue-specific changes in expression dominating the injury responses of each tissue, injury-induced changes in gene expression were nonetheless shared between the two axon-regenerative CNS regions that were not shared with the non-regenerative region. These included similar temporal patterns of gene expression and over 300 injury-responsive genes. Many of these genes and their associated cellular functions had previously been associated with injury responses of multiple tissues, both neural and non-neural, from different species, thereby demonstrating deep phylogenetically conserved commonalities between successful CNS axon regeneration and tissue regeneration in general. Further analyses implicated the KEGG adipocytokine signaling pathway, which links leptin with metabolic and gene regulatory pathways, and a novel gene regulatory network with genes regulating chromatin accessibility at its core, as important hubs in the larger network of injury response genes involved in successful CNS axon regeneration.ConclusionsThis study identifies deep, phylogenetically conserved commonalities between CNS axon regeneration and other examples of successful tissue regeneration and provides new targets for studying the molecular underpinnings of successful CNS axon regeneration, as well as a guide for distinguishing pro-regenerative injury-induced changes in gene expression from detrimental ones in mammals.

Expression of vesicular glutamate transporter 2 and 3 and glutamate receptor 1 and 2 mRNAs in the retina of adult laughing doves (Streptopelia senegalensis): An in situ hybridization study

The retina possesses few types of neurons so; it is considered an excellent model for understanding the neural mechanisms underlying basic neural information processing in the brain. Glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system and retina. The present study was carried out to characterize the expression pattern of vesicular glutamate transporter 2 (Vglut2) and 3 (Vglut3) and glutamate receptor 1 (GluR1) and 2 (GluR2) mRNAs in the retina of adult laughing dove (Streptopelia senegalensis) by RT-PCR and in situ hybridization histochemistry. The cerebellum of adult laughing dove was used as a positive control in this study. Vglut2 mRNA was highly expressed only in the granular layer of the cerebellum while Vglut3 mRNA was weakly expressed only in the Purkinje cells layer. In the retina, Vglut2 mRNA was highly expressed in the ganglion cell layer and moderately expressed in the inner nuclear layer while Vglut3 mRNA was moderately expressed only in the inner nuclear layer. GluR1 mRNA was intensely expressed in the Purkinje cells layer while GluR2 mRNA signals were highly detectable in both granular and Purkinje cells layers of the cerebellum. In the retina, moderate expression of GluR1 and intense expression of GluR2 was found in both ganglion cell layer and the internal half of inner nuclear layer mostly amacrine cells. These results suggest that some retinal neuronal cells in the adult laughing dove are glutamatergic. Therefore, GluR1 and 2 are suggested as useful markers for glutamatergic retinal neuronal cells in the adult laughing doves.