Mechanisms of Satellite Oligodendroglia-Neuron Interaction in Brain Maturation

About This Grant

Mechanisms of Satellite Oligodendroglia-Neuron Interaction in Brain Maturation Abstract During postnatal brain maturation, neurons acquire functional properties that are essential for shaping cognitive and motor functions. Disruptions in this maturation process, whether due to injury or genetic abnormalities, are implicated in a range of neurological disorders, including autism, cerebral palsy, and epilepsy, significantly impacting quality of life. A major obstacle to developing therapies that promote or support healthy brain maturation is the limited understanding of the underlying mechanisms. Glial cells play a crucial role in neuronal maturation by supporting synapse formation, synaptic pruning, and axonal myelination, which are all essential for establishing functional neural circuits. Recently, using a mouse genetic Cre-LoxP system, we found that oligodendroglia transfer nuclear and ribosomal material to neurons. This process, termed oligodendroglia-neuron material transfer (ONMT), occurs in the cortex, hippocampal dentate gyrus and striatum during a critical period of neuronal maturation. We identified satellite oligodendroglia (SOL) forming nuclear pairs with receiving neurons and SOL-neuron pairs with loss of plasma membrane integrity, suggesting a possibility of direct ONMT. The role of SOL-neuron interaction and ONMT in neuronal maturation, as well as the mechanisms involved, remain largely unknown. This exploratory proposal will test the hypothesis that during brain maturation SOL transfer material to neurons through direct internuclear contact. In Aim 1, we will identify neurons receiving SOL-derived material during maturation and explore the triggers of ONMT. To achieve this, we will use spatial transcriptomics to capture single-cell transcriptional profiles of SOL-neuron nuclear pairs in both healthy developing cortex and in neuroinflammatory conditions that promote SOL-neuron interactions and ONMT. In Aim 2, we will investigate whether SOL transfer material to neurons via an internuclear mechanism. This will involve using 2-photon live imaging to track SOL migration, SOL-neuron interactions, material transfer, and SOL fate during postnatal maturation. Our study aims to uncover novel insights into the previously unrecognized process of ONMT during a critical period of neuronal maturation, paving the way for targeted therapeutic strategies to promote brain maturation in children with developmental delays.