The Structure and Function of Glial Networks: Beyond the Neuronal Connections / 神经科学通报·英文版

Glial cells, consisting of astrocytes, oligodendrocyte lineage cells, and microglia, account for >50% of the total number of cells in the mammalian brain. They play key roles in the modulation of various brain activities under physiological and pathological conditions. Although the typical morphological features and characteristic functions of these cells are well described, the organization of interconnections of the different glial cell populations and their impact on the healthy and diseased brain is not completely understood. Understanding these processes remains a profound challenge. Accumulating evidence suggests that glial cells can form highly complex interconnections with each other. The astroglial network has been well described. Oligodendrocytes and microglia may also contribute to the formation of glial networks under various circumstances. In this review, we discuss the structure and function of glial networks and their pathological relevance to central nervous system diseases. We also highlight opportunities for future research on the glial connectome.

Roles of NG2 Glia in Cerebral Small Vessel Disease / 神经科学通报·英文版

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Interactions Between Astrocytes and Oligodendroglia in Myelin Development and Related Brain Diseases / 神经科学通报·英文版

Astrocytes (ASTs) and oligodendroglial lineage cells (OLGs) are major macroglial cells in the central nervous system. ASTs communicate with each other through connexin (Cx) and Cx-based network structures, both of which allow for quick transport of nutrients and signals. Moreover, ASTs interact with OLGs through connexin (Cx)-mediated networks to modulate various physiological processes in the brain. In this article, following a brief description of the infrastructural basis of the glial networks and exocrine factors by which ASTs and OLGs may crosstalk, we focus on recapitulating how the interactions between these two types of glial cells modulate myelination, and how the AST-OLG interactions are involved in protecting the integrity of the blood-brain barrier (BBB) and regulating synaptogenesis and neural activity. Recent studies further suggest that AST-OLG interactions are associated with myelin-related diseases, such as multiple sclerosis. A better understanding of the regulatory mechanisms underlying AST-OLG interactions may inspire the development of novel therapeutic strategies for related brain diseases.

Coordinated Regulation of Myelination by Growth Factor and Amino-acid Signaling Pathways / 神经科学通报·英文版

Myelin-forming oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS) are essential for structural and functional homeostasis of nervous tissue. Albeit with certain similarities, the regulation of CNS and PNS myelination is executed differently. Recent advances highlight the coordinated regulation of oligodendrocyte myelination by amino-acid sensing and growth factor signaling pathways. In this review, we discuss novel insights into the understanding of differential regulation of oligodendrocyte and Schwann cell biology in CNS and PNS myelination, with particular focus on the roles of growth factor-stimulated RHEB-mTORC1 and GATOR2-mediated amino-acid sensing/signaling pathways. We also discuss recent progress on the metabolic regulation of oligodendrocytes and Schwann cells and the impact of their dysfunction on neuronal function and disease.

Immunological Markers for Central Nervous System Glia / 神经科学通报·英文版

Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.

Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes / 神经科学通报·英文版

Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.

Rol de la neuroglia en el trastorno del espectro autista / Role of neuroglia in autism spectrum disorder

RESUMEN: El trastorno del espectro autista (TEA) se caracteriza por presentar déficits persistentes en la comunicación y en la interacción social. Además, patrones de comportamiento, intereses o actividades de tipo restrictivo o repetitivo. Su etiología es compleja y heterogenia, y los mecanismos neurobiológicos que dan lugar al fenotipo clínico aún no se conocen por completo. Las investigaciones apuntan a factores genéticos y ambientales que afectan el cerebro en desarrollo. Estos avances coinciden con un aumento en la comprensión de las funciones fisiológicas y el potencial patológico de la neuroglia en el sistema nervioso central (SNC) que llevó a la noción de la contribución fundamental de estas células en el TEA. Así, el objetivo de este artículo fue revisar brevemente los factores de riesgo clave asociados al TEA y luego, explorar la contribución de la neuroglia en este trastorno. Se destaca el rol de los astrocitos, los microglocitos y los oligodendrocitos en el control homeostático del SNC, en la regulación inmunitaria del cerebro y en la mielinización axonal, así como el mal funcionamiento y las alteraciones morfológicas de estas células en los cerebros autistas.

SUMMARY: Autism spectrum disorder (ASD) is characterized by persistent deficits in communication and social interaction, as well as restrictive or repetitive activities or interests. Its etiology is complex and heterogeneous, and the neurobiological mechanisms that give rise to the clinical phenotype are not yet fully understood. Research points to genetic and environmental factors that affect the developing brain. These advances are consistent with an enhanced understanding of the physiological functions and pathological potential of neuroglia in the central nervous system (CNS) which supports the conclusion of the contribution of these cells in ASD. Therefore, the objective of this article was to briefly review the key risk factors associated with ASD and then explore the contribution of glia in this disorder. The role of astrocytes, microgliocytes and oligodendrocytes in the homeostatic control of the CNS in the immune regulation of the brain and in axonal myelination, as well as malfunction and morphological alterations of these cells in autistic brains are emphasized.

Claudin-1 and Claudin-3 as Molecular Regulators of Myelination in Leukoaraiosis Patients

OBJECTIVES: Leukoaraiosis is described as white matter lesions that are associated with cognitive dysfunction, neurodegenerative disorders, etc. Myelin depletion is a salient pathological feature of, and the loss of oligodendrocytes is one of the most robust alterations evident in, white matter degeneration. Recent studies have revealed that claudin proteins are aberrantly expressed in leukoaraiosis and regulate oligodendrocyte activity. However, the roles of claudin-1 and claudin-3 in oligodendrocytes and leukoaraiosis are still not well-defined. METHODS: Quantitative polymerase chain reaction was used to measure the expression of claudin-1 (CLDN1), claudin-3 (CLDN3), and myelinogenesis-related genes such as myelin basic protein (MBP), proteolipid protein (PLP), oligodendrocyte transcription factor 2 (OLIG2), and SRY-box transcription factor 10 (SOX10) in leukoaraiosis patients (n=122) and healthy controls (n=122). The expression of claudin-1 and claudin-3 was either ectopically silenced or augmented in Oli-neu oligodendrocytes, and colony formation, apoptosis, and migration assays were performed. Finally, the expression of myelin proteins was evaluated by western blotting. RESULTS: Our results revealed that in addition to SOX10, the expression levels of claudin-1, claudin-3, and myelinogenesis-related proteins were prominently downregulated in leukoaraiosis patients, compared to those in healthy controls. Furthermore, the growth and migration of Oli-neu cells were downregulated upon silencing claudin-1 or claudin-3. However, the overexpression of claudin-1 or claudin-3 resulted in the reduction of the degree of apoptosis in Oli-neu cells. In addition, claudin-1 and claudin-3 promoted the expression of MBP, OLIG2, PLP, and SOX10 at the translational level. CONCLUSION: Our data has demonstrated that the abnormal expression of claudin-1 and claudin-3 regulates the pathological progression of leukoaraiosis by governing the viability and myelination of oligodendrocytes. These findings provide novel insights into the regulatory mechanisms underlying the roles of claudin-1 and claudin-3 in leukoaraiosis.

Chronic Exposure to Hypoxia Inhibits Myelinogenesis and Causes Motor Coordination Deficits in Adult Mice / 神经科学通报·英文版

Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER

Pinocembrin Promotes OPC Differentiation and Remyelination via the mTOR Signaling Pathway / 神经科学通报·英文版

The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Biological characteristics and functions of NG2-glia / 生理学报

NG2-glia are a major type of glial cells that are widely distributed in the central nervous system (CNS). Under physiological conditions, they mainly differentiate into oligodendrocytes and contribute to the myelination of axons, so they are generally called oligodendrocyte progenitor cells. Emerging evidence suggests that NG2-glia not only act as the precursors of oligodendrocytes but also possess many other biological properties and functions. For example, NG2-glia can form synapse with neurons and participate in energy metabolism and immune regulation. Under pathological conditions, NG2-glia can also differentiate into astrocytes, Schwann cells and even neurons, which are involved in CNS injury and repair. Therefore, a deeper understanding of the biological characteristics and functions of NG2-glia under physiological and pathological conditions will be helpful for the treatment of CNS injury and disease. This article reviews the recent advances in the biological characteristics and functions of NG2-glia.

Protective effect of transplantation of human oligodendrocyte precursor cells in a rat model of white matter injury / 中国当代儿科杂志

OBJECTIVE@#To study the effect of human oligodendrocyte precursor cell (hOPC) transplantation in the treatment of white matter injury (WMI).@*METHODS@#Neonatal rats were randomly divided into a sham-operation group, a model group, and a transplantation group (@*RESULTS@#The place navigation test using the Morris water maze showed that the model group had a significantly longer escape latency than the sham-operation group, and compared with the model group, the transplantation group had a significant reduction in escape latency (@*CONCLUSIONS@#Intrathecal hOPC transplantation may alleviate neurological injury and promote remyelination in a rat model of WMI.

Altered oligodendrocytes in spinal enlargements of streptozotocin diabetic rats / Oligodendrocitos alterados en la intumescencia espinal de ratas diabéticas con estreptozotocina

SUMMARY: Disturbances of sensory and motor nerve conduction velocity in the spinal cord as well as degenerated myelin sheaths are observed in diabetic patients and animal models. Indeed, oligodendrocytes (OLs), which are important neuroglial cells, generate myelin in the central nervous system. Spinal enlargement, including cervical and lumbar enlargements, innervates all limbs. Thus, the purposes of this study were to examine and compare the ultrastructural alterations of OLs in spinal enlargements of streptozotocin (STZ)- induced diabetic rats and controls. Thirteen male Sprague-Dawley rats were induced with STZ in citrate buffer and six control rats were injected with the same buffer solution. All rats were sacrificed after inductions at four (short-term DM) and twenty-four weeks (long-term DM). The selected spinal enlargements were processed for transmission electron microscopy. The OL alterations in both the cervical and lumbar enlargements were apparently the same. In short-term DM, the nuclei of OLs became swelled with chromatin clumping. Cytoplasmic organelles were moderately damaged. In long-term DM, OLs contained shrinkage nuclei with thick heterochromatin clumping. Severely degenerated mitochondria with disrupted cristae and broken membranes were observed. Moreover, distended and fragmented rough endoplasmic reticulum were observed, and large clear areas were present in the cytoplasm. Additionally, the loosening, splitting, and destruction of myelin lamellae were found. This study can provide important preliminary information about the alteration of OLs in the spinal cords of diabetic patients, which might be involve in the impairments of sensory and motor conduction velocities in these individuals.

RESUMEN: En pacientes diabéticos y modelos animales se observan alteraciones de la velocidad de conducción nerviosa sensorial y motora en la médula espinal, así como vainas de mielina degeneradas. De hecho, los oligodendrocitos (OL), que son importantes células neurogliales, generan mielina en el sistema nervioso central. La intumescencia espinal, a nivel cervical y lumbar, inerva los miembros. Por lo tanto, los propósitos de este estudio fueron examinar y comparar las alteraciones ultraestructurales de los OL en la intumescencia espinal de ratas diabéticas inducidas por estreptozotocina (STZ) y controles. Se indujeron trece ratas macho Sprague-Dawley con STZ en tampón citrato y se inyectaron seis ratas de control con la misma solución tampón. Todas las ratas se sacrificaron después de la inducción a las cuatro (DM a corto plazo) y a las veinticuatro semanas (DM a largo plazo). Las ampliaciones de la columna seleccionadas se procesaron para microscopía electrónica de transmisión. Las alteraciones de OL en las intumescencias cervical y lumbar eran aparentemente las mismas. En la DM a corto plazo, los núcleos de los OL se hincharon con la acumulación de cromatina. Los orgánulos citoplasmáticos sufrieron daños moderados. En la DM a largo plazo, los OL contenían núcleos de contracción con aglutinación de heterocromatina gruesa. Se observaron mitocondrias severamente degeneradas con crestas y membranas rotas. Además, se observó un retículo endoplásmico rugoso distendido y fragmentado, y estaban presentes grandes áreas claras en el citoplasma. Además, se encontraron el aflojamiento, la división y la destrucción de las laminillas de mielina. Este estudio puede proporcionar información preliminar importante sobre la alteración de los OL en la médula espinal de los pacientes diabéticos, que podría estar involucrada en las alteraciones de las velocidades de conducción sensorial y motora en estos individuos.

Autophagy Mediates Astrogenesis in Adult Hippocampal Neural Stem Cells

Neural stem cells (NSCs) have the ability to self-renew and differentiate into neurons, oligodendrocytes, and astrocytes. Highly dynamic nature of NSC differentiation requires the intimate involvement of catabolic processes such as autophagy. Autophagy is a major intracellular degradation pathway necessary for cellular homeostasis and remodeling. Autophagy is important for mammalian development and its role in neurogenesis has recently drawn much attention. However, little is known about how autophagy is associated with differentiation of NSCs into other neural lineages. Here, we report that autophagy plays a critical role in differentiation of adult rat hippocampal neural stem (HCN) cells into astrocytes. During differentiation, autophagy flux peaked at early time points, and remained high. Pharmacological or genetic suppression of autophagy by stable knockdown of Atg7, LC3 or CRISPR-Cas9-mediated knockout (KO) of p62 impaired astrogenesis, while reintroduction of p62 recovered astrogenesis in p62 KO HCN cells. Taken together, our findings suggest that autophagy plays a key role in astrogenesis in adult NSCs.

Effects of Carpobrotus edulis Extract on Oxidative Stress and 158N Oligodendrocyte Death / 生物医学与环境科学（英文）

OBJECTIVE@#Age-related diseases, including neurodegenerative diseases, are associated with oxidative stress and lipid peroxidation, and increase the levels of cholesterol auto-oxidation products such as 7β-hydroxycholesterol (7β-OHC). Thus, it is imperative to identify agents that can prevent 7β-OHC-induced side-effects.@*METHODS@#We evaluated the potential protective effects of Carpobrotus edulis ethanol-water extract (EWe) on murine oligodendrocytes (158N) cultured in the absence or presence of 7β-OHC (20 μg/mL, 24 h). The cells were incubated with EWe (20-200 µg/mL) 2 h before 7β-OHC treatment. Mitochondrial activity and cell growth were evaluated with the MTT assay. Photometric methods were used to analyze antioxidant enzyme [catalase (CAT) and glutathione peroxidase (GPx)] activities and the generation of lipid and protein oxidation products [malondialdehyde (MDA), conjugated diene (CD), and carbonylated proteins (CPs)].@*RESULTS@#Treatment with 7β-OHC induced cell death and oxidative stress (reflected by alteration in CAT and SOD activities). Overproduction of lipid peroxidation products (MDA and CDs) and CPs was also reported. The cytotoxic effects associated with 7β-OHC were attenuated by 160 μg/mL of EWe of C. edulis. Cell death induced by 7β-OHC treatment was ameliorated, GPx and CAT activities were restored to normal, and MDA, CD, and CP levels were reduced following C. edulis extract treatment.@*CONCLUSION@#These data demonstrate the protective activities of C. edulis EWe against 7β-OHC-induced disequilibrium in the redox status of 158N cells, indicative of the potential role of this plant extract in the prevention of neurodegenerative diseases.

Effect of propofol on myelin basic protein expression and myelination of oligodendrocytes in neonatal SD rats / 南方医科大学学报

OBJECTIVE@#To investigate the effects of different doses of propofol on myelin basic protein (MBP) synthesis and myelination of oligodendrocytes in neonatal SD rats.@*METHODS@#A total of 57 neonatal SD rats (7 days old) were randomly divided into control group (=13), vehicle (fat emulsion) group (=5), and 25, 50 and 100 mg/kg propofol groups (=13 in each group). Eight hours after a single intraperitoneal injection of propofol or the vehicle, the rats were examined for expressions of mRNA, caspase-3 mRNA, cleaved caspase-3 and MBP in the brain tissues using qPCR and Western blotting. Immunofluorescence assay was used to detect the apoptosis of the oligodendrocytes at 8 h after the injection and the myelination of the corpus callosum and internal capsule at 24 h.@*RESULTS@#Compared with the control group, the neonatal rats with propofol injections showed significantly down-regulated expressions of mRNA and MBP protein in the brain tissue ( < 0.05). Propofol dose-dependently increased the transcription level of caspase-3 and the protein levels of cleaved caspase-3 at 8 h after the injection ( < 0.05). Propofol injection significantly increased the apoptosis of the oligodendrocytes, and the effect was significantly stronger in 50 and 100 mg/kg groups than in 25 mg/kg group ( < 0.05). At 24 h after propofol injection, myelin formation was significantly decreased in the corpus callosum of the neonatal rats in 100 mg/kg propofol group and in the internal capsule in 50 and 100 mg/kg groups ( < 0.05).@*CONCLUSIONS@#In neonatal SD rats, propofol can dose-dependently promote oligodendrocyte apoptosis, decrease MBP expressions in the brain, and suppress myelin formation in the corpus callosum and the internal capsule.

Quantitative Proteomic Analysis Reveals Impaired Axonal Guidance Signaling in Human Postmortem Brain Tissues of Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.

Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes / 한국실험동물학회지

In this study, we observed chronological changes in the immunoreactivity and expression level of myelin basic protein (MBP), one of the most abundant proteins in the central nervous system, in the hippocampus of Zucker diabetic fatty (ZDF) rats and their control littermates (Zucker lean control; ZLC). In the ZLC group, body weight steadily increased with age; the body weight of the ZDF group, however, peaked at 30 weeks of age, and subsequently decreased. Based on the changes of body weight, animals were divided into the following six groups: early (12-week), middle (30-week), and chronic (52-week) diabetic groups and their controls. MBP immunoreactivity was found in the alveus, strata pyramidale, and lacunosum-moleculare of the CA1 region, strata pyramidale and radiatum of the CA3 region, and subgranular zone, polymorphic layer, and molecular layer of the dentate gyrus. MBP immunoreactivity was lowest in the hippocampus of 12-week-old rats in the ZLC group, and highest in 12-week-old rats in the ZDF group. Diabetes increased MBP levels in the 12-week-old group, while MBP immunoreactivity decreased in the 30-week-old group. In the 52-week-old ZLC and ZDF groups, MBP immunoreactivity was detected in the hippocampus, similar to the 30-week-old ZDF group. Western blot results corroborated with immunohistochemical results. These results suggested that changes in the immunoreactivity and expression of MBP in the hippocampus might be a compensatory response to aging, while the sustained levels of MBP in diabetic animals could be attributed to a loss of compensatory responses in oligodendrocytes.

The Relationship between Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and the Rubella Virus

No abstract available.

Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination / 神经科学通报·英文版

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.