ArticleDevelopmental biology2013
Cyclin dependent kinase 5 is required for the normal development of oligodendrocytes and myelin formation.
Article in Developmental biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Cerebrospinal fluid neutral lipids predict progression from mild cognitive impairment to Alzheimer's disease.GeroScience · 2024Article
- Article
- Cannabinoids modulate proliferation, differentiation, and migration signaling pathways in oligodendrocytes.European archives of psychiatry and clinical neuroscience · 2022Article
- Casein Kinase 2 Signaling in White Matter Stroke.Frontiers in molecular biosciences · 2022Review
- Three decades of Cdk5.Journal of biomedical science · 2021Review
- Review
- Cyclin-dependent Kinase 18 Promotes Oligodendrocyte Precursor Cell Differentiation through Activating the Extracellular Signal-Regulated Kinase Signaling Pathway.Neuroscience bulletin · 2019Article
- An ImprovedFrontiers in neuroscience · 2019Article
- Tau in Oligodendrocytes Takes Neurons in Sickness and in Health.International journal of molecular sciences · 2018Review
- Oligodendrocyte-specific loss of Cdk5 disrupts the architecture of nodes of Ranvier as well as learning and memory.Experimental neurology · 2018Article
- Thioredoxin-1 Protects Spinal Cord from Demyelination Induced by Methamphetamine through Suppressing Endoplasmic Reticulum Stress and Inflammation.Frontiers in neurology · 2018Article
- Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease.Molecular neurodegeneration · 2017Article
- Active Cdk5 Immunoprecipitation and Kinase Assay.Bio-protocol · 2017Article
- Inhibition of Drp1 hyper-activation is protective in animal models of experimental multiple sclerosis.Experimental neurology · 2017Article
- Dynamic Partitioning of Synaptic Vesicle Pools by the SNARE-Binding Protein Tomosyn.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- The Role of Cdk5 in Alzheimer's Disease.Molecular neurobiology · 2016Review
- The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Intracellular Protein Shuttling: A Mechanism Relevant for Myelin Repair in Multiple Sclerosis?International journal of molecular sciences · 2015Review
- CDK5 is a major regulator of the tumor suppressor DLC1.The Journal of cell biology · 2014Article
- Cyclin-dependent kinase 5 mediates adult OPC maturation and myelin repair through modulation of Akt and GsK-3β signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
The development of oligodendrocytes, the myelinating cells of the vertebrate CNS, is regulated by a cohort of growth factors and transcription factors. Less is known about the signaling pathways that integrate extracellular signals with intracellular transcriptional regulators to control oligodendrocyte development. Cyclin dependent kinase 5 (Cdk5) and its co-activators play critical roles in the regulation of neuronal differentiation, cortical lamination, neuronal cell migration and axon outgrowth. Here we demonstrate a previously unrecognized function of Cdk5 in regulating oligodendrocyte maturation and myelination. During late embryonic development Cdk5 null animals displayed a reduction in the number of MBP+ cells in the spinal cord, but no difference in the number of OPCs. To determine whether the reduction of oligodendrocytes reflected a cell-intrinsic loss of Cdk5, it was selectively deleted from Olig1+ oligodendrocyte lineage cells. In Olig1(Cre/+); Cdk5(fl/fl) conditional mutants, reduced levels of expression of MBP and PLP mRNA were observed throughout the CNS and ultrastructural analyses demonstrated a significant reduction in the proportion of myelinated axons in the optic nerve and spinal cord. Pharmacological inhibition or RNAi knockdown of Cdk5 in vitro resulted in the reduction in oligodendrocyte maturation, but had no effect on OPC cell proliferation. Conversely, over-expression of Cdk5 promoted oligodendrocyte maturation and enhanced process outgrowth. Consistent with this data, Cdk5(-/-) oligodendrocytes developed significantly fewer primary processes and branches than control cells. Together, these findings suggest that Cdk5 function as a signaling integrator to regulate oligodendrocyte maturation and myelination.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.