Glutamate signaling via the AMPAR subunit GluR4 regulates oligodendrocyte progenitor cell migration in the developing spinal cord
- Piller, M., Werkman, I.L., Brown, E.A., Latimer, A.J., Kucenas, S.
- The Journal of neuroscience : the official journal of the Society for Neuroscience 41(25): 5353-5371 (Journal)
- Registered Authors
- Brown, Evan, Kucenas, Sarah, Latimer, Andrew
- MeSH Terms
- Cell Differentiation/physiology
- Cell Movement/physiology
- Glutamic Acid/metabolism*
- Oligodendrocyte Precursor Cells/metabolism*
- Receptors, AMPA/metabolism*
- Signal Transduction/physiology
- Spinal Cord/embryology*
- 33975920 Full text @ J. Neurosci.
Piller, M., Werkman, I.L., Brown, E.A., Latimer, A.J., Kucenas, S. (2021) Glutamate signaling via the AMPAR subunit GluR4 regulates oligodendrocyte progenitor cell migration in the developing spinal cord. The Journal of neuroscience : the official journal of the Society for Neuroscience. 41(25):5353-5371.
Oligodendrocyte progenitor cells (OPC) are specified from discrete precursor populations during gliogenesis and migrate extensively from their origins, ultimately distributing throughout the brain and spinal cord during early development. Subsequently, a subset of OPCs differentiates into mature oligodendrocytes, which myelinate axons. This process is necessary for efficient neuronal signaling and organism survival. Previous studies have identified several factors that influence OPC development, including excitatory glutamatergic synapses that form between neurons and OPCs during myelination. However, little is known about how glutamate signaling affects OPC migration prior to myelination. In this study, we use in vivo, time-lapse imaging in zebrafish in conjunction with genetic and pharmacological perturbation to investigate OPC migration and myelination when the GluR4A ionotropic glutamate receptor subunit is disrupted. In our studies, we observed that gria4a mutant embryos and larvae displayed abnormal OPC migration and altered dorsoventral distribution in the spinal cord. Genetic mosaic analysis confirmed that these effects were cell-autonomous, and we identified that voltage-gated calcium channels were downstream of glutamate receptor signaling in OPCs and could rescue the migration and myelination defects we observed when glutamate signaling was perturbed. These results offer new insights into the complex system of neuron-OPC interactions and reveal a cell-autonomous role for glutamatergic signaling in OPCs during neural development.SIGNIFICANCE STATEMENT:The migration of oligodendrocyte progenitor cells (OPC) is an essential process during development that leads to uniform oligodendrocyte distribution and sufficient myelination for central nervous system function. Here we demonstrate that the AMPA receptor subunit GluR4A is an important driver of OPC migration in vivo and that activated voltage-gated calcium channels are downstream of glutamate receptor signaling in mediating this migration.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes