Neuron-Oligodendrocyte Communication Underlying Myelin Distribution in the Neocortex

Summary

This project investigates the mechanistic principles of neuron-oligodendrocyte communication that control neuron-type specific myelination and its regeneration in the neocortex, aiming to understand myelin's role in circuit function and dysfunction.

What they want

The project proposes to: 1) use molecular profiling of oligodendrocytes and cortical neuron subtypes across different cortical layers to map transcriptome differences and generate a molecular interactome of candidates for genes mediating neuron-OL communication; 2) employ a screen to identify candidates able to induce or repress myelination; 3) investigate membrane protein composition of myelinated and unmyelinated axonal segments of a specific neuronal class at subcellular resolution and study whether long unmyelinated regions are differentially enriched for functionally-relevant structures; and 4) investigate the molecular mechanisms that control cell-type specific adaptive remodeling of myelin and its regeneration after demyelination.

Deliverables

Mapped differences in transcriptome of oligodendrocytes and cortical neuron subtypes
Molecular interactome of candidate genes for neuron-oligodendrocyte communication
Identified candidates able to induce or repress myelination
Understanding of membrane protein composition of myelinated and unmyelinated axonal segments
Analysis of functional structure enrichment in unmyelinated regions
Understanding of molecular mechanisms controlling cell-type specific adaptive remodeling of myelin and its regeneration

Technical requirements

Molecular profiling of oligodendrocytes and cortical neuron subtypes
Screen to identify candidates for myelination induction/repression
Subcellular resolution investigation of membrane protein composition