Development Of Central Nervous System Research Articles

Deletion of the Sodium-Dependent Glutamate Transporter GLT-1 in Maturing Oligodendrocytes Attenuates Myelination of Callosal Axons During a Postnatal Phase of Central Nervous System Development.

The sodium-dependent glutamate transporter GLT-1 (EAAT2, SLC1A2) has been well-described as an important regulator of extracellular glutamate homeostasis in the central nervous system (CNS), a function that is performed mainly through its presence on astrocytes. There is, however, increasing evidence for the expression of GLT-1 in CNS cells other than astrocytes and in functional roles that are mediated by mechanisms downstream of glutamate uptake. In this context, GLT-1 expression has been reported for both neurons and oligodendrocytes (OLGs), and neuronal presynaptic presence of GLT-1 has been implicated in the regulation of glutamate uptake, gene expression, and mitochondrial function. Much less is currently known about the functional roles of GLT-1 expressed by OLGs. The data presented here provide first evidence that GLT-1 expressed by maturing OLGs contributes to the modulation of developmental myelination in the CNS. More specifically, using inducible and conditional knockout mice in which GLT-1 was deleted in maturing OLGs during a peak period of myelination (between 2 and 4 weeks of age) revealed hypomyelinated characteristics in the corpus callosum of preferentially male mice. These characteristics included reduced percentages of smaller diameter myelinated axons and reduced myelin thickness. Interestingly, this myelination phenotype was not found to be associated with major changes in myelin gene expression. Taken together, the data presented here demonstrate that GLT-1 expressed by maturing OLGs is involved in the modulation of the morphological aspects associated with CNS myelination in at least the corpus callosum and during a developmental window that appears of particular vulnerability in males compared to females.

TBIO-02. Mapping the origins of pediatric brain tumors to cell type lineages in the developing cerebellum.

Understanding the cellular origins of cerebellar tumors at single cell resolution may help identify novel therapeutic vulnerabilities to overcome current impediments in pediatric neuro-oncology. One approach to answer this important question involves the mapping of tumor profiles onto normal embryonal central nervous system development. Previous attempts in this regard focused on integrating human tumor data with developing mouse cerebellum atlases, however, these approaches were inherently limited due to species-specific differences. In order to address this critical issue, we use a high resolution developing human cerebellum single cell atlas in order to compare to extended bulk and single cell transcriptomes profiles from pediatric solid tumors. In result, we provide novel and confirmatory findings for the cellular association of medulloblastoma SHH, Group3 and Group4 as well as pilocytic astrocytoma, using comprehensive approaches to decipher the cellular composition and map the origins of childhood brain tumors. We also shed light on the cellular origins of posterior fossa ependymoma and radiation-induced glioma (secondary tumor, occurring after medulloblastoma). As a common feature among the tumor similarity to normal cell types, we identify gradients of differentiation, starting from early progenitor cells to more differentiated cell states, observed in all cerebellar tumor entities investigated at single cell level; thus reflecting possible lineages of origin. Pertaining to clinical application, we identified specific developmental genes shared between cerebellar lineages and associated tumors, and tumor-specific genes absent in all cerebellar lineages. These two categories of genes comprise candidate lineage markers for faithful modeling and, if absent from other organ systems after birth, could become an important source of potential therapeutic targets. Importantly, all analysis results are publicly available via an interactive online user interface (brain-match.org) that serves as an open valuable resource for the scientific community.

A Link Between Gut Microbiota and Schizophrenia

IntroductionMicroorganisms distributed in our tissues and fluids make up the human microbiota. During our lifetime, gastrointestinal microbiota acts as an important modulator of brain development and, in turn, adult behavior and health. Immune response may be triggered by gut microbiota, releasing mediators that penetrate the blood-brain barrier (BBB).ObjectivesUnderstanding if gut microbiota can influence schizophrenia pathogenesis. Clarifying how gut microbiota can influence schizophrenia treatment, and vice-versa.MethodsPubMed database search, with “gut microbiota and schizophrenia” keyword expression. Eight articles published in the last ten years were selected among the most recent best match results. Reference lists of articles were reviewed to identify additional articles.ResultsThere could be an association between the development of gut microbiota starting during pregnancy and schizophrenia pathogenesis, through an immune-mediated process. Schwarz et al. (2018) investigated the differences in faecal microbiota between individuals with first-episode psychosis and controls. They found psychotic patients to have an increased amount of Lactobacillus bacteria. Yuan et al. (2018) studied microbiota changes in patients with schizophrenia, before and after treatment. Individuals diagnosed with schizophrenia had less faecal Bifidobacterium, Escherichia coli and Lactobacillus. After treatment with risperidone, there was a significant increase in the amount of fecal Bifidobacterium and E. Coli.ConclusionsMicroorganisms living inside our gastrointestinal tract are vital for proper central nervous system (CNS) development. Patients with schizophrenia have anomalies in the composition of the microbiota. It remains unclear if microbiota changes after treatment further influence the course of the disease.DisclosureNo significant relationships.

Thirty Years' History since the Discovery of Pax6: From Central Nervous System Development to Neurodevelopmental Disorders.

Pax6 is a sequence-specific DNA binding transcription factor that positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system (CNS). As indicated by the morphological and functional abnormalities in spontaneous Pax6 mutant rodents, Pax6 plays pivotal roles in various biological processes in the CNS. At the initial stage of CNS development, Pax6 is responsible for brain patterning along the anteroposterior and dorsoventral axes of the telencephalon. Regarding the anteroposterior axis, Pax6 is expressed inversely to Emx2 and Coup-TF1, and Pax6 mutant mice exhibit a rostral shift, resulting in an alteration of the size of certain cortical areas. Pax6 and its downstream genes play important roles in balancing the proliferation and differentiation of neural stem cells. The Pax6 gene was originally identified in mice and humans 30 years ago via genetic analyses of the eye phenotypes. The human PAX6 gene was discovered in patients who suffer from WAGR syndrome (i.e., Wilms tumor, aniridia, genital ridge defects, mental retardation). Mutations of the human PAX6 gene have also been reported to be associated with autism spectrum disorder (ASD) and intellectual disability. Rodents that lack the Pax6 gene exhibit diverse neural phenotypes, which might lead to a better understanding of human pathology and neurodevelopmental disorders. This review describes the expression and function of Pax6 during brain development, and their implications for neuropathology.

Lutein levels in arterial cord blood correlate with neurotrophic calcium binding S100B protein in healthy preterm and term newborns

BackgroundS100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns.MethodsWe conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns.ResultsS100B and LT showed a pattern of concentration characterized by higher levels (P < 0.01, for all) at 33-36 weeks gestation (GA) followed by a progressive decrease (P < 0.01, for all) from 37 onwards with a dip at term. Both S100B and LT were gender-dependent with significantly (P < 0.01, for all) higher levels in females in preterm and term groups. S100B (R = 0.68; P < 0.001) and LT (R = 0.40; P = 0.005) correlated with GA at sampling. A positive significant correlation (R = 0.87; P < 0.001) between S100B and LT was found.ConclusionsThe present data showing a correlation between S100B and LT supports the notion of a LT trophic role in the CNS. Further investigations in high-risk infants are needed to elucidate LT involvement in the pathophysiological cascade of events leading to CNS development and damage.

Effects of methylphenidate after a long period of discontinuation include changes in exploratory behavior and increases brain activities of Na+,K+-ATPase and acetylcholinesterase

Methylphenidate (MPH) has been widely misused by children and adolescents who do not meet all diagnostic criteria for attention-deficit/hyperactivity disorder. Since it is not yet known whether MPH can be administered in childhood without consequences in adulthood, in the present study we proposed to investigate the effects of chronic early treatment with MPH after a long period of discontinuation. Wistar male rats were injected with MPH (2 mg/kg, intraperitoneally) or saline solution once daily from 15th to 44th day of life. Two months after the last MPH administration, we evaluated the animal’s performances on a battery of behavior tests. We also tested Na+,K+-ATPase and acetylcholinesterase activities in prefrontal cortex and hippocampus, which may be associated with behavior. Rats treated with MPH during peri-adolescence show changes in exploratory behavior in adulthood in the open field but not in the elevated plus maze and light–dark transition tests. MPH-treated rats showed a lower latency to find the platform in the training phase, as well as a better performance in the test phase in the Morris water maze test. No differences were observed in the object recognition index and working memory. Acetylcholinesterase was increased in prefrontal cortex and hippocampus, while Na+,K+-ATPase was increased only in hippocampus. These findings provide additional evidence that early-life exposure to MPH can have complex effects in adulthood and new basis for understanding the behavioral and neurochemical consequences associated with chronic use of MPH during the development of central nervous system.

The Specific Mechanism of TREM2 Regulation of Synaptic Clearance in Alzheimer's Disease.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Synaptic dysfunction is an integral feature of AD pathophysiology and a significant factor in early cognitive impairment in AD. Microglia, which are intrinsic immune cells in the central nervous system, play important regulatory roles in the process of synapse formation. Microglia can refine synaptic connections through synaptic clearance to ensure accurate synaptic transmission. Synaptic clearance is not only existed during central nervous system development but also aberrantly activated during AD pathology. However, the mechanisms of synaptic clearance in AD remain to be investigated. TREM2 is involved in the synaptic clearance of microglia, acting alone or with other molecules, such as apolipoprotein E (APOE). In addition, C1q is essential for microglia-mediated synaptic clearance. In this review, we systematically summarized the potential mechanisms of microglia involved in synaptic clearance, comprehensively reviewed the role of TREM2 in microglia regulating synaptic clearance and proposed our hypothesis that TREM2 interacts with APOE and C1q to promote synaptic clearance. This review provides new insights into the role of TREM2 regulation in microglia synaptic clearance and provides potential prospects for the treatment of AD.

PP2A-associated tau hyperphosphorylation was involved in sevoflurane induced neonatal neurotoxicity.

The effects of sevoflurane anesthesia on childhood neurodevelopment and adult brain function have attracted increasing scientific attentions. However, the exact mechanisms underlying hyperphosphorylation of tau protein in sevoflurane induced abnormalities in central nervous system (CNS) development, particularly in the hippocampus, have not been fully determined. We utilized molecular biological and behavioral approaches to compare the changes in cognitive function in mice exposed to repeated sevoflurane during the neonatal stage, and to assess whether PP2A-associated tau hyperphosphorylation is involved in sevoflurane induced neonatal neurotoxicity. We reported that mice anesthetized with repeated sevoflurane during the neonatal period caused cognitive dysfunction during the adulthood. More importantly, we found that hyperphosphorylation of tau protein and decreased level of protein phosphatase 2A (PP2A) were detected in the hippocampus of mice after neonatal exposure of sevoflurane. Meanwhile, GSK-3β activity was found to be increased with repeated sevoflurane exposure, but not for more than 2weeks. Our results suggest that PP2A-associated hyperphosphorylation of tau protein might contribute to sevoflurane induced developmental neurotoxicity. These findings could provide a theoretical basis for the safely usage of sevoflurane in pediatric surgeries, and offer a valuable reference and potential therapeutic targets for the development of neuroprotective drugs.

Cdk5-mediated JIP1 phosphorylation regulates axonal outgrowth through Notch1 inhibition

BackgroundActivated Cdk5 regulates a number of processes during nervous system formation, including neuronal differentiation, growth cone stabilization, and axonal growth. Cdk5 phosphorylates its downstream substrates located in axonal growth cones, where the highly expressed c-Jun N-terminal kinase (JNK)-interacting protein1 (JIP1) has been implicated as another important regulator of axonal growth. In addition, stringent control of the level of intracellular domain of Notch1 (Notch1-IC) plays a regulatory role in axonal outgrowth during neuronal differentiation. However, whether Cdk5-JIP1-Notch1 cooperate to regulate axonal outgrowth, and the mechanism of such joint contribution to this pathway, is presently unknown, and here we explore their potential interaction.ResultsOur interactome screen identified JIP1 as an interactor of p35, a Cdk5 activator, and we sought to explore the relationship between Cdk5 and JIP1 on the regulation of axonal outgrowth. We demonstrate that JIP1 phosphorylated by Cdk5 at Thr205 enhances axonal outgrowth and a phosphomimic JIP1 rescues the axonal outgrowth defects in JIP1−/− and p35−/− neurons. Axonal outgrowth defects caused by the specific increase of Notch1 in JIP1−/− neurons are rescued by Numb-mediated inhibition of Notch1. Finally, we demonstrate that Cdk5 phosphorylation of JIP1 further amplifies the phosphorylation status of yet another Cdk5 substrate E3-ubiquitin ligase Itch, resulting in increased Notch1 ubiquitination.ConclusionsOur findings identify a potentially critical signaling axis involving Cdk5-JIP1-Itch-Notch1, which plays an important role in the regulation of CNS development. Future investigation into the way this pathway integrates with additional pathways regulating axonal growth will further our knowledge of normal central nervous system development and pathological conditions.

Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to Enhance 3D Structures of the Central Nervous System.

Pluripotent stem cell-derived organoid models of the central nervous system represent one of the most exciting areas in in vitro tissue engineering. Classically, organoids of the brain, retina and spinal cord have been generated via recapitulation of in vivo developmental cues, including biochemical and biomechanical. However, a lesser studied cue, bioelectricity, has been shown to regulate central nervous system development and function. In particular, electrical stimulation of neural cells has generated some important phenotypes relating to development and differentiation. Emerging techniques in bioengineering and biomaterials utilise electrical stimulation using conductive polymers. However, state-of-the-art pluripotent stem cell technology has not yet merged with this exciting area of bioelectricity. Here, we discuss recent findings in the field of bioelectricity relating to the central nervous system, possible mechanisms, and how electrical stimulation may be utilised as a novel technique to engineer “next-generation” organoids.

Significant Sex Differences in the Efficacy of the CSF1R Inhibitor-PLX5622 on Rat Brain Microglia Elimination.

Microglia play pivotal roles in central nervous system development, homeostasis, responses to trauma, and neurodegenerative and neuropsychiatric disorders with significant sex-bias in their symptoms and prevalence. Survival of the microglia in adult brains depends on the expression of the colony-stimulating factor 1 receptor (CSF1R). The inhibition of CSF1R by brain-permeant PLX5622 in the chow eliminates, within 5–10 days, ~90% of the microglia in female and male mice, thereby enabling the investigation of the roles of the microglia in health and pathological mice models. Because of a prevailing “impression” that PLX5622 is ineffective in rats, it has hardly been used in studies of adult rats. Here, we report that effective microglia elimination by PLX5622-chow in rats is highly sex-dependent. Our observations provide missing information for the limited use and interpretation of PLX5622 in biomedical studies of the microglia in rat models. The sex differences that are too often overlooked must be carefully considered and clearly emphasized.

Microglia, the Sentinel of Brain in the Evolution of Nervous System from Invertebrate to Vertebrate: A Short Review

The presence of microglial cells as resident macrophage population in the Central Nervous System (CNS) is well documented from the study of repairing of lesions in CNS that varies widely throughout the animal kingdom. The existence of neuroglia cells similar to vertebrate microglia and small mobile phagocytes and hemocytes were documented from ganglia of some invertebrate animal models like leech (H. medicinalis), insects (P. americana and D. melanogaster) and mollusca (M. edulis). Neuronal replacement and migration of immunocompetent cells (macrophage, microglia, ependymal cells etc.) after surgical lesions in CNS of non-mammals (fishes, reptiles and aves) are much restricted to specific neurogenic niches associated to the neural regeneration and migration of cells in invertebrates. Microglial presence is largely restricted in the optic tract of fish and amphibian ganglionic cells because they have a surprising capacity to regenerate their neurons after lesions. Hence the CNS of both invertebrates and vertebrates contain microglia like mononuclear phagocytes, ensheathing glia and reticular glia, which indicate about the evolutionary conserved innate immune response to maintain CNS development and health. But the presence and gradual changes in the structure and function of microglia and neuron-microglia relationship in the CNS along the phylogeny need to be focused thoroughly.

Evolution, characterization and expression analysis of Sox gene family in rainbow trout (Oncorhynchus mykiss)

The Sox transcription factor family plays an important role in various biological processes such as animal sex determination and multiple organ development. We used online databases to analyze the gene structure, chemical characteristics, and evolutionary relationship of Sox family genes through bioinformatics, and we studied the expression profiles and regulatory mechanisms of Sox family genes. A total of 29 rainbow trout Sox genes were identified. The phylogenetic analysis found that Sox genes of rainbow trout were clustered in seven subfamilies (B1, B2, C, D, E, F and H), and the gene structure of each subfamily was relatively conserved. Furthermore, Sox1, Sox4, Sox6, Sox8, Sox9, Sox11, Sox17, Sox18, and Sox19 developed into two copies, which might be the result of teleost fish-specific genome replication. Multiple HMG box domain alignments indicated that the motifs for all Sox sequences are conserved. Gene expression studies reveal that Sox expression is tissue-specific and that multiple Sox genes are involved in rainbow trout gonad and central nervous system development. Our study provides valuable information on the evolution of teleosts, and will also help to further research the functional characteristics of Sox genes.

Impact of Nuclear Envelope Stress on Physiological and Pathological Processes in Central Nervous System.

The nuclear envelope (NE) separates genomic DNA from the cytoplasm and provides the molecular platforms for nucleocytoplasmic transport, higher-order chromatin organization, and physical links between the nucleus and cytoskeleton. Recent studies have shown that the NE is often damaged by various stresses termed "NE stress", leading to critical cellular dysfunction. Accumulating evidence has revealed the crucial roles of NE stress in the pathology of a broad spectrum of diseases. In the central nervous system (CNS), NE dysfunction impairs neural development and is associated with several neurological disorders, such as Alzheimer's disease and autosomal dominant leukodystrophy. In this review, the structure and functions of the NE are summarized, and the concepts of NE stress and NE stress responses are introduced. Additionally, the significant roles of the NE in the development of CNS and the mechanistic connections between NE stress and neurological disorders are described.

Vascular Regulation of Developmental Neurogenesis.

Evolutionary studies indicate that the nervous system evolved prior to the vascular system, but the increasing complexity of organisms prompted the vascular system to emerge in order to meet the growing demand for oxygen and nutrient supply. In recent years, it has become apparent that the symbiotic communication between the nervous and the vascular systems goes beyond the exclusive covering of the demands on nutrients and oxygen carried by blood vessels. Indeed, this active interplay between both systems is crucial during the development of the central nervous system (CNS). Several neural-derived signals that initiate and regulate the vascularization of the CNS have been described, however less is known about the vascular signals that orchestrate the development of the CNS cytoarchitecture. Here, we focus on reviewing the effects of blood vessels in the process of neurogenesis during CNS development in vertebrates. In mammals, we describe the spatiotemporal features of vascular-driven neurogenesis in two brain regions that exhibit different neurogenic complexity in their germinal zone, the hindbrain and the forebrain.

P446. The Microbiota-Gut-Brain-Axis in Early life: The Temporal Relation Between Gut Microbial Development Over the First Year and Subsequent Social-Emotional Development up to 36 Months in Healthy Infants

Early life colonization with microorganisms is critically important for healthy gastro-intestinal and, through the gut-brain-axis, central nervous system development. So far, associations between infant gut microbiome and cognitive outcomes at 2 or 3 years have been observed, however, always based on isolated timepoints, lacking resolution on the temporal development of this relation.

The Neurodevelopmental Disorders Associated Gene Rnf113a Regulates Survival and Differentiation Properties of Neural Stem Cells.

RNF113A (Ring Finger Protein 113A) is genetically associated with autism spectrum disorders and X-linked trichothiodystrophy (TTD) syndrome. Loss-of-function mutations in human RNF113A are causally linked to TTD, which is characterized by abnormal development of the central nervous system (CNS) and mental retardation. How the loss of RNF113A activity affects brain development is not known. Here we identify Rnf113a1 as a critical regulator of cell death and neurogenesis during mouse brain development. Rnf113a1 gene exhibits widespread expression in the embryonic CNS. Knockdown studies in embryonic cortical neural stem/progenitor cells (NSCs) and the mouse cortex suggest that Rnf113a1 controls the survival, proliferation, and differentiation properties of progenitor cells. Importantly, Rnf113a1 deficiency triggers cell apoptosis via a combined action on essential regulators of cell survival, including p53, Nupr1, and Rad51. Collectively, these observations establish Rnf113a1 as a regulatory factor in CNS development and provide insights into its role in neurodevelopmental defects associated with TTD and autism.

Maternal Hypoxia Increases the Excitability of Neurons in the Entorhinal Cortex and Dorsal Hippocampus of Rat Offspring.

Prenatal hypoxia is a widespread condition that causes various disturbances in later life, including aberrant central nervous system development, abnormalities in EEG rhythms, and susceptibility to seizures. Hypoxia in rats on the 14th day of embryogenesis (E14) disrupts cortical neuroblast radial migration, mainly affecting the progenitors of cortical glutamatergic neurons but not GABAergic interneurons or hippocampal neurons. Thus, hypoxia at this time point might affect the development of the neocortex to a greater extent than the hippocampus. In the present study, we investigated the long-term effects of hypoxia on the properties of the pyramidal neurons in the hippocampus and entorhinal cortex (EC) in 3-week-old rats subjected to hypoxia on E14. We observed a reduction in the total number of NeuN-positive neurons in EC but not in the CA1 field of the hippocampus, indicating an increased cell loss in EC. However, the principal neuron electrophysiological characteristics were altered in the EC and hippocampus of animals exposed to hypoxia. The whole-cell patch-clamp recordings revealed a similar increase in input resistance in neurons from the hippocampus and EC. However, the resting membrane potential was increased in the EC neurons only. The recordings of field postsynaptic potentials (fPSPs) in the CA1 hippocampal area showed that both the threshold currents inducing fPSPs and population spikes were lower in hypoxic animals compared to age-matched controls. Using the dosed electroshock paradigm, we found that seizure thresholds were lower in the hypoxic group. Thus, the obtained results suggest that maternal hypoxia during the generation of the pyramidal cortical neurons leads to the increased excitability of neuronal circuitries in the brain of young rats. The increased excitability can be attributed to the changes in intrinsic neuronal properties.

Reduced inhibition underlies early life LPS exposure induced-cognitive impairment: Prevention by environmental enrichment

Early life immune activation has negative effects on the development of central nervous system and cognitive function, yet the underlying mechanism remains unclear. Increasing evidence has demonstrated that inflammation induces changes in microglia morphology, which lead to excessive synaptic pruning and improper function of neural circuits. Therefore, we hypothesized that early immune activation induced microglia activation, contributing to synaptic and cognitive impairments in adolescent mice. To establish the animal model of early immune activation, pups received a single intraperitoneal injection of 100 μg/kg lipopolysaccharide (LPS) on postnatal 10 (P10). Environmental enrichment (EE) was conducted four hours per day during P10-P38. Behavioral tests were performed by open field (P39), elevated plus-maze (P40) and Y maze tests (P41). The protein levels of glutamic acid decarboxylas67 (GAD67), parvalbumin (PV), vesicular gaba amino acid transporter (vGAT) and vesicular glutamate transporters (vGLUT1) were determined in the hippocampi and medial prefrontal cortex (mPFC). The protein levels of nuclear factor κB (NF-κB)/p65, NF-κB/p50, interleukin-1β (IL-1β), tumor necrosis factor - ɑ (TNF-ɑ) were determined in the hippocampi. The dendritic spine density was evaluated in the CA1 of the hippocampus. In our study, we showed that early life LPS exposure induced microglia activation and excessive inhibitory synapse engulfment, decreased number of perisomatic puncta on both inhibitory PV interneurons and excitatory neurons, which might contribute to excitation/inhibition imbalance, dendritic spine loss, and cognitive impairment in adolescent mice. Notably, EE rescued most of these abnormalities and improved cognitive impairment. In conclusion, our study demonstrated that reduced inhibition might contribute to early life LPS exposure induced-cognitive impairment. We also provided the possibility of the protective role of EE in rescuing these long-term adverse effects.

Gfap transgenic medaka as a novel reporter line for neural stem cells

Radial glial cells (RGCs) play an essential role in developing, maintaining, and repairing the central nervous system (CNS). However, a specific reporter line of RGCs is limited in medaka. Glial fibrillary acid protein (GFAP) is abundant in teleost CNS, including the brain and spinal cord, and is a possible candidate for a marker for RGCs in medaka CNS. We generated a transgenic medaka in which enhanced green fluorescent protein (EGFP) expression is regulated under putative medaka gfap regulatory elements. We observed EGFP expression in the CNS of live larval and juvenile medaka through the transparent body of the See-through medaka strain. Histological analysis for juvenile and adult Tg(gfap:EGFP) medaka showed that EGFP was expressed in GFAP-positive cells in the telencephalon, optic tectum, retina, and spinal cord. We further found another EGFP expressing cells in the optic tectum and retina. These cells are possibly neuroepithelial-like stem cells, deducing from the distribution of these EGFP-positive cells. We concluded that this reporter line would be valuable in the investigation of neural stem cell function during the development and regeneration of medaka CNS visualizing two types of neural stem cells, RGCs and neuroepithelial-like stem cells.