Search

During cortical development and throughout adulthood, oligodendrocytes add myelin internodes to glutamatergic projection neurons and GABAergic inhibitory neurons. In addition to directing node of Ranvier formation, to enable saltatory conduction and influence action potential transit time, oligodendrocytes support axon health by communicating with axons via the periaxonal space and providing metabolic support that is particularly critical for healthy ageing. In this review we outline the timing of oligodendrogenesis in the developing mouse and human cortex and describe the important role that oligodendrocytes play in sustaining and modulating neuronal function. We also provide insight into the known and speculative impact that myelination has on cortical axons and their associated circuits during the developmental critical periods and throughout life, particularly highlighting their life-long role in learning and remembering.

Primary cilia are small microtubule‐based organelles capable of transducing signals from growth factor receptors embedded in the cilia membrane. Developmentally, oligodendrocyte progenitor cells (OPCs) express genes associated with primary cilia assembly, disassembly, and signaling, however, the importance of primary cilia for adult myelination has not been explored. We show that OPCs are ciliated in vitro and in vivo, and that they disassemble their primary cilia as they progress through the cell cycle. OPC primary cilia are also disassembled as OPCs differentiate into oligodendrocytes. When kinesin family member 3a (Kif3a), a gene critical for primary cilium assembly, was conditionally deleted from adult OPCs in vivo (Pdgfrα‐CreER™:: Kif3a fl/fl transgenic mice), OPCs failed to assemble primary cilia. Kif3a‐deletion was also associated with reduced OPC proliferation and oligodendrogenesis in the corpus callosum and motor cortex and a progressive impairment of fine motor coordination., Main Points OPCs disassemble primary cilia upon cell cycle re‐entry.Deletion of Kif3a from OPCs prevents primary cilia assembly and reduces OPC proliferation.Deletion of Kif3a from adult OPCs in vivo reduces oligodendrogenesis and impairs motor function.

Myelin and axon losses are associated with cognitive decline in healthy ageing but are worse in people diagnosed with tauopathy. To determine whether tauopathy is also associated with enhanced myelin plasticity, we evaluated the behaviour of OPCs in mice that expressed a human pathological variant of microtubule‐associated protein tau (MAPTP301S ). By 6 months of age (P180), MAPTP301S mice overexpressed hyperphosphorylated tau and had developed reactive gliosis in the hippocampus but had not developed overt locomotor or memory impairment. By performing cre‐lox lineage tracing of adult OPCs, we determined that the number of newborn oligodendrocytes added to the hippocampus, entorhinal cortex and fimbria was equivalent in control and MAPTP301S mice prior to P150. However, between P150 and P180, significantly more new oligodendrocytes were added to these regions in the MAPTP301S mouse brain. This large increase in new oligodendrocyte number was not the result of increased OPC proliferation, nor did it alter oligodendrocyte density in the hippocampus, entorhinal cortex or fimbria, which was equivalent in P180 wild‐type and MAPTP301S mice. Furthermore, the proportion of hippocampal and fimbria axons with myelin was unaffected by tauopathy. However, the proportion of myelinated axons that were ensheathed by immature myelin internodes was significantly increased in the hippocampus and fimbria of P180 MAPTP301S mice, when compared with their wild‐type littermates. These data suggest that MAPTP301S transgenic mice experience significant oligodendrocyte turnover, with newborn oligodendrocytes compensating for myelin loss early in the development of tauopathy., Mice overexpressing a pathological variant of human microtubule‐associated protein tau (MAPT P301S) experience increased oligodendrogenesis in the hippocampus, entorhinal cortex and fimbria between 5 and 6 months of age. Total oligodendrocyte and oligodendrocyte progenitor cell number, axon density and the per cent of myelinated axons remain normal, though there is an increase in newly generated myelin, suggesting that oligodendrocyte turnover occurs early in the development of tauopathy.

Background Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease, characterised by oligodendrocyte death and demyelination. Oligodendrocyte progenitor cells can differentiate into new replacement oligodendrocytes; however, remyelination is insufficient to protect neurons from degeneration in people with MS. We previously reported that 4 weeks of daily low-intensity repetitive transcranial magnetic stimulation (rTMS) in an intermittent theta-burst stimulation (iTBS) pattern increased the number of new myelinating oligodendrocytes in healthy adult mice. This study translates this rTMS protocol and aims to determine its safety and tolerability for people living with MS. We will also perform magnetic resonance imaging (MRI) and symptom assessments as preliminary indicators of myelin addition following rTMS. Methods Participants (N = 30, aged 18–65 years) will have a diagnosis of relapsing-remitting or secondary progressive MS. ≤2 weeks before the intervention, eligible, consenting participants will complete a physical exam, baseline brain MRI scan and participant-reported MS symptom assessments [questionnaires: Fatigue Severity Scale, Quality of Life (AQoL-8D), Hospital Anxiety and Depression Scale; and smartphone-based measures of cognition (electronic symbol digit modalities test), manual dexterity (pinching test, draw a shape test) and gait (U-Turn test)]. Participants will be pseudo-randomly allocated to rTMS (n=20) or sham (placebo; n=10), stratified by sex. rTMS or sham will be delivered 5 days per week for 4 consecutive weeks (20 sessions, 6 min per day). rTMS will be applied using a 90-mm circular coil at low-intensity (25% maximum stimulator output) in an iTBS pattern. For sham, the coil will be oriented 90° to the scalp, preventing the magnetic field from stimulating the brain. Adverse events will be recorded daily. We will evaluate participant blinding after the first, 10th and final session. After the final session, participants will repeat symptom assessments and brain MRI, for comparison with baseline. Participant-reported assessments will be repeated at 4-month post-allocation follow-up. Discussion This study will determine whether this rTMS protocol is safe and tolerable for people with MS. MRI and participant-reported symptom assessments will serve as preliminary indications of rTMS efficacy for myelin addition to inform further studies. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12619001196134. Registered on 27 August 2019

Oligodendrocyte progenitor cells (OPCs) express protocadherin 15 (Pcdh15), a member of the cadherin superfamily of transmembrane proteins. Little is known about the function of Pcdh15 in the central nervous system (CNS), however, Pcdh15 expression can predict glioma aggression and promote the separation of embryonic human OPCs immediately following a cell division. Herein, we show that Pcdh15 knockdown significantly increases extracellular signal-related kinase (ERK) phosphorylation and activation to enhance OPC proliferation in vitro. Furthermore, Pcdh15 knockdown elevates Cdc42-Arp2/3 signalling and impairs actin kinetics, reducing the frequency of lamellipodial extrusion and slowing filopodial withdrawal. Pcdh15 knockdown also reduces the number of processes supported by each OPC and new process generation. Our data indicate that Pcdh15 is a critical regulator of OPC proliferation and process motility, behaviours that characterise the function of these cells in the healthy CNS, and provide mechanistic insight into the role that Pcdh15 might play in glioma progression.

Neuronal activity is a potent extrinsic regulator of oligodendrocyte generation and central nervous system myelination. Clinically, repetitive transcranial magnetic stimulation (rTMS) is delivered to noninvasively modulate neuronal activity; however, the ability of rTMS to facilitate adaptive myelination has not been explored. By performing cre‐lox lineage tracing, to follow the fate of oligodendrocyte progenitor cells in the adult mouse brain, we determined that low intensity rTMS (LI‐rTMS), administered as an intermittent theta burst stimulation, but not as a continuous theta burst or 10 Hz stimulation, increased the number of newborn oligodendrocytes in the adult mouse cortex. LI‐rTMS did not alter oligodendrogenesis per se, but instead increased cell survival and enhanced myelination. These data suggest that LI‐rTMS can be used to noninvasively promote myelin addition to the brain, which has potential implications for the treatment of demyelinating diseases such as multiple sclerosis., Main Points The impact that low intensity repetitive transcranial magnetic stimulation (LI‐rTMS) has on cells of the oligodendrocyte lineage is stimulation frequency and cell‐stage specific.LI‐rTMS does not affect oligodendrocyte progenitor cell proliferation or density.LI‐rTMS, delivered in an intermittent theta burst pattern, promotes the survival of premyelinating oligodendrocytes and enhances myelin internode extension by newly myelinating oligodendrocytes.

Maternal alcohol consumption throughout pregnancy can result in long term behavioural deficits in offspring. However, less is known about the impact of alcohol during the periconceptional period (PC). The aim of this study was to examine the effect of PC ethanol (PC:EtOH) exposure on long term cognitive function; including memory and anxiety. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol;vol) or a control diet from 4 days prior to mating until day 4 of pregnancy. Separate cohorts of animals were tested at 6 months (adult) or 15–18 months of age (aged). Offspring underwent a series of behavioural tests to assess anxiety, spatial and recognition memory. The hippocampus was collected, and mRNA expression of epigenetic modifiers and genes implicated in learning and memory were examined. PC:EtOH exposure resulted in a subtle anxiety like behaviour in adult female offspring with a significant reduction in directed exploring/head dipping behaviour during holeboard testing. In aged male offspring, PC:EtOH exposure resulted in a tendency for increased directed exploring/head dipping behaviour during holeboard testing. No differences between treatments were observed in the elevated plus maze. Aged female offspring exposed to PC:EtOH demonstrated short term spatial memory impairment (P < 0.05). PC:EtOH resulted in an upregulation of hippocampal mRNA expression of bdnf, grin2a and grin2b at 18 months of age along with increased expression of epigenetic modifiers (dnmt1, dnmt3a and hdac2). In conclusion, PC:EtOH can lead to sex specific anxiety-like behaviour and impairments in spatial memory and altered hippocampal gene expression.

Central nervous system myelination increases action potential conduction velocity. However, it is unclear how myelination is coordinated to ensure the temporally precise arrival of action potentials and facilitate information processing within cortical and associative circuits. Here, we show that myelin sheaths, supported by mature oligodendrocytes, remain plastic in the adult mouse brain and undergo subtle structural modifications to influence action potential conduction velocity. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration is independent of oligodendrogenesis and robustly alters action potential conduction velocity. Because aptitude in the spatial learning task was found to correlate with action potential conduction velocity in the fimbria-fornix pathway, modifying the axon-glial configuration may be a mechanism that facilitates learning in the adult mouse brain.

Low-density lipoprotein receptor-related protein 1 (LRP1) is a large, endocytic cell surface receptor that is highly expressed by oligodendrocyte progenitor cells (OPCs) and LRP1 expression is rapidly downregulated as OPCs differentiate into oligodendrocytes (OLs). We report that the conditional deletion of Lrp1 from adult mouse OPCs (Pdgfrα-CreER :: Lrp1fl/fl) increases the number of newborn, mature myelinating OLs added to the corpus callosum and motor cortex. As these additional OLs extend a normal number of internodes that are of a normal length, Lrp1-deletion increases adult myelination. OPC proliferation is also elevated following Lrp1 deletion in vivo, however, this may be a secondary, homeostatic response to increased OPC differentiation, as our in vitro experiments show that LRP1 is a direct negative regulator of OPC differentiation, not proliferation. Deleting Lrp1 from adult OPCs also increases the number of newborn mature OLs added to the corpus callosum in response to cuprizone-induced demyelination. These data suggest that the selective blockade of LRP1 function on adult OPCs may enhance myelin repair in demyelinating diseases such as multiple sclerosis., Graphical Abstract LRP1 regulates adult oligodendrogenesis and remyelination.

It is well established that maternal undernutrition and micronutrient deficiencies can lead to altered development and behaviour in offspring. However, few studies have explored the implications of maternal Mg deficiency and programmed behavioural and neurological outcomes in offspring. We used a model of Mg deficiency (prior to and during pregnancy and lactation) in CD1 mice to investigate if maternal Mg deficiency programmed changes in behaviour and NMDAR subunit expression in offspring. Hippocampal tissue was collected at postnatal day 2 (PN2), PN8, PN21 and 6 months, and protein expression of NMDAR subunits GluN1, GluN2A and GluN2B was determined. At 6 months of age, offspring were subject to behavioural tasks testing aspects of anxiety-like behaviour, memory, and neophobia. Maternal hypomagnesemia was associated with increased GluN1, GluN2A and GluN2B subunit expression in female offspring at 6 months, but decreased GluN1 and GluN2A expression in males. The GluN2B:GluN2A expression ratio was increased in both sexes. Male (but not female) offspring from Mg-deficient dams showed anxiety-like behaviour, with reduced head dips (Suok test), and reduced exploration of open arms (elevated plus maze). Both male and female offspring from Mg-deficient dams also showed impaired recognition memory (novel object test). These findings suggest that maternal Mg deficiency can result in behavioural deficits in adult life, and that these changes may be related to alterations in hippocampal NMDA receptor expression.

In Alzheimer's disease, amyloid plaque formation is associated with the focal death of oligodendrocytes and soluble amyloid β impairs the survival of oligodendrocytes in vitro. However, the response of oligodendrocyte progenitor cells (OPCs) to early amyloid pathology remains unclear. To explore this, we performed a histological, electrophysiological, and behavioral characterization of transgenic mice expressing a pathological form of human amyloid precursor protein (APP), containing three single point mutations associated with the development of familial Alzheimer's disease (PDGFB‐APPSw.Ind, also known as J20 mice). PDGFB‐APPSw.Ind transgenic mice had impaired survival from weaning, were hyperactive by 2 months of age, and developed amyloid plaques by 6 months of age, however, their spatial memory remained intact over this time course. Hippocampal OPC density was normal in P60‐P180 PDGFB‐APPSw.Ind transgenic mice and, by performing whole‐cell patch‐clamp electrophysiology, we found that their membrane properties, including their response to kainate (100 µM), were largely normal. However, by P100, the response of hippocampal OPCs to GABA was elevated in PDGFB‐APPSw.Ind transgenic mice. We also found that the nodes of Ranvier were shorter, the paranodes longer, and the myelin thicker for hippocampal axons in young adult PDGFB‐APPSw.Ind transgenic mice compared with wildtype littermates. Additionally, oligodendrogenesis was normal in young adulthood, but increased in the hippocampus, entorhinal cortex, and fimbria of PDGFB‐APPSw.Ind transgenic mice as pathology developed. As the new oligodendrocytes were not associated with a change in total oligodendrocyte number, these cells are likely required for cell replacement., Myelin structure is altered in the hippocampus of mice overexpressing a pathological variant of the human amyloid precursor protein (PDGFB‐APPSw.Ind; APP mice). APP mice have longer paranodes, thicker myelin, and shorter nodes of Ranvier than wildtype mice by 3 months of age, however, total axon density and the proportion of axons that were myelinated was normal. Between 4 and 6 months of age, APP mice have more new oligodendrocytes added to the hippocampus, entorhinal cortex, and fimbria, while total oligodendrocyte and oligodendrocyte progenitor cell density remained stable, suggesting that new oligodendrocytes may be produced to replace oligodendrocytes lost due to amyloid pathology.

Myelination of central nervous system axons increases action potential conduction velocity and increases the speed of information transfer. However, it is unclear whether myelination optimizes action potential conduction to achieve synchronicity and facilitate information processing within cortical and associative circuits. Here we show that myelin sheaths remain plastic in the adult mouse and undergo subtle structural modifications to influence action potential conduction. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration, which is independent of oligodendrogenesis, tunes conduction velocity to increase the synchronicity of action potential conduction. One Sentence Summary The activity-dependent modulation of nodes of Ranvier and the periaxonal space allows central conduction to be tuned to achieve synchronicity.

The amyloid-β precursor protein (APP) is a transmembrane protein that is widely expressed within the central nervous system (CNS). While the pathogenic dysfunction of this protein has been extensively studied in the context of Alzheimer's disease, its normal function is poorly understood, and reports have often appeared contradictory. In this study we have examined the role of APP in regulating neurogenesis in the adult mouse brain by comparing neural stem cell proliferation, as well as new neuron number and morphology between APP knockout mice and C57bl6 controls. Short-term EdU administration revealed that the number of proliferating EdU+ neural progenitor cells and the number of PSA-NCAM+ neuroblasts produced in the SVZ and dentate gyrus were not affected by the life-long absence of APP. However, by labelling newborn cells with EdU and then following their fate over-time, we determined that ~48% more newly generated EdU+ NeuN+ neurons accumulated in the granule cell layer of the olfactory bulb and ~57% more in the dentate gyrus of young adult APP knockout mice relative to C57bl6 controls. Furthermore, proportionally fewer of the adult-born olfactory bulb granule neurons were calretinin+. To determine whether APP was having an effect on neuronal maturation, we administered tamoxifen to young adult Nestin-CreERT2::Rosa26-YFP and Nestin-CreERT2::Rosa26-YFP::APP-knockout mice, fluorescently labelling ~80% of newborn (EdU+) NeuN+ dentate granule neurons formed between P75 and P105. Our analysis of their morphology revealed that neurons added to the hippocampus of APP knockout mice have shorter dendritic arbors and only half the number of branch points as those generated in C57bl6 mice. We conclude that APP reduces the survival of newborn neurons in the olfactory bulb and hippocampus, but that it does not influence all neuronal subtypes equally. Additionally, APP influences dentate granule neuron maturation, acting as a robust regulator of dendritic extension and arborisation.

Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring. Rats were exposed to a liquid diet containing ethanol (EtOH) (12.5% vol/vol) or a control diet from 4 days before mating until 4 days after mating. PC:EtOH had no effect on alcohol preference in either sex. At 15 months of age, however, male PC:EtOH offspring consumed more high-fat food when compared with male control offspring, but this preference was not observed in females. Expression of the dopamine receptor type 1 (Drd1a) was lower in the VTA of male PC:EtOH offspring compared with their control counterparts. There was no effect of PC:EtOH on mRNA expression of the µ-opioid receptor, tyrosine hydroxylase (Th), dopamine receptor type 2 (Drd2) or dopamine active transporter (Slc6a3). These data support the hypothesis that periconceptional alcohol exposure can alter expression of key components of the mesolimbic reward pathway and heighten the preference of offspring for palatable foods and may therefore increase their propensity towards diet-induced obesity. These results highlight the importance of alcohol avoidance when planning a pregnancy.

Cell membrane thyroid hormone (TH) transport can be facilitated by the monocarboxylate transporter 8 (MCT8), encoded by the solute carrier family 16 member 2 (SLC16A2) gene. Human mutations of the gene, SLC16A2, result in the X-linked-inherited psychomotor retardation and hypomyelination disorder, Allan-Herndon-Dudley syndrome (AHDS). We posited that abrogating MCT8-dependent TH transport limits oligodendrogenesis and myelination. We show that human oligodendrocytes (OL), derived from the NKX2.1-GFP human embryonic stem cell (hESC) reporter line, express MCT8. Moreover, treatment of these cultures with DITPA (an MCT8-independent TH analog), up-regulates OL differentiation transcription factors and myelin gene expression. DITPA promotes hESC-derived OL myelination of retinal ganglion axons in co-culture. Pharmacological and genetic blockade of MCT8 induces significant OL apoptosis, impairing myelination. DITPA treatment limits OL apoptosis mediated by SLC16A2 down-regulation primarily signaling through AKT phosphorylation, driving myelination. Our results highlight the potential role of MCT8 in TH transport for human OL development and may implicate DITPA as a promising treatment for developmentally-regulated myelination in AHDS.

The low density lipoprotein-receptor related protein 1 (LRP1) is a large endocytic cell surface receptor that is known to interact with a variety of ligands, intracellular adaptor proteins and other cell surface receptors to regulate cellular behaviours ranging from proliferation to cell fate specification, migration, axon guidance, and lipid metabolism. A number of studies have demonstrated that LRP1 is expressed in the brain, yet it is unclear which central nervous system cell types express LRP1 during development and in adulthood. Herein we undertake a detailed study of LRP1 expression within the mouse brain and spinal cord, examining a number of developmental stages ranging from embryonic day 13.5 to postnatal day 60. We report that LRP1 expression in the brain peaks during postnatal development. On a cellular level, LRP1 is expressed by radial glia, neuroblasts, microglia, oligodendrocyte progenitor cells (OPCs), astrocytes and neurons, with the exception of parvalbumin+ interneurons in the cortex. Most cell populations exhibit stable expression of LRP1 throughout development; however, the proportion of OPCs that express LRP1 increases significantly from ~69% at E15.5 to ~99% in adulthood. We also report that LRP1 expression is rapidly lost as OPCs differentiate, and is absent from all oligodendrocytes, including newborn oligodendrocytes. While LRP1 function has been primarily examined in mature neurons, these expression data suggest it plays a more critical role in glial cell regulation-where expression levels are much higher.

Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol) ethanol (EtOH) or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult) or 15 months (Aged) of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

Prenatal exposure to high levels of alcohol is strongly associated with poor cognitive outcomes particularly in relation to learning and memory. It is also becoming more evident that anxiety disorders and anxiety-like behaviour can be associated with prenatal alcohol exposure. This study used a rat model to determine if prenatal exposure to a relatively small amount of alcohol would result in anxiety-like behaviour and to determine if this was associated with morphological changes in the basolateral amygdala. Pregnant Sprague Dawley rats were fed a liquid diet containing either no alcohol (Control) or 6% (vol/vol) ethanol (EtOH) throughout gestation. Male and Female offspring underwent behavioural testing at 8 months (Adult) or 15 months (Aged) of age. Rats were perfusion fixed and brains were collected at the end of behavioural testing for morphological analysis of pyramidal neuron number and dendritic morphology within the basolateral amygdala. EtOH exposed offspring displayed anxiety-like behaviour in the elevated plus maze, holeboard and emergence tests. Although sexually dimorphic behaviour was apparent, sex did not impact anxiety-like behaviour induced by prenatal alcohol exposure. This increase in anxiety – like behaviour could not be attributed to a change in pyramidal cell number within the BLA but rather was associated with an increase in dendritic spines along the apical dendrite which is indicative of an increase in synaptic connectivity and activity within these neurons. This study is the first to link increases in anxiety like behaviour to structural changes within the basolateral amygdala in a model of prenatal ethanol exposure. In addition, this study has shown that exposure to even a relatively small amount of alcohol during development leads to long term alterations in anxiety-like behaviour.

In the central nervous system (CNS) platelet derived growth factor receptor alpha (PDGFRα) is expressed exclusively by oligodendrocyte progenitor cells (OPCs), making the Pdgfrα promoter an ideal tool for directing transgene expression in this cell type. Two Pdgfrα-CreERT2 mouse lines have been generated for this purpose which, when crossed with cre-sensitive reporter mice, allow the temporally restricted labelling of OPCs for lineage-tracing studies. These mice have also been used to achieve the deletion of CNS-specific genes from OPCs. However the ability of Pdgfrα-CreERT2 mice to induce cre-mediated recombination in PDGFRα+ cell populations located outside of the CNS has not been examined. Herein we quantify the proportion of PDGFRα+ cells that become YFP-labelled following Tamoxifen administration to adult Pdgfrα-CreERT2::Rosa26-YFP transgenic mice. We report that the vast majority (>90%) of PDGFRα+ OPCs in the CNS, and a significant proportion of PDGFRα+ stromal cells within the bone marrow (~38%) undergo recombination and become YFP-labelled. However, only a small proportion of the PDGFRα+ cell populations found in the sciatic nerve, adrenal gland, pituitary gland, heart, gastrocnemius muscle, kidney, lung, liver or intestine become YFP-labelled. These data suggest that Pdgfrα-CreERT2 transgenic mice can be used to achieve robust recombination in OPCs, while having a minimal effect on most PDGFRα+ cell populations outside of the CNS.