# Molecular and genetic decoding of neuron-glial interactions

> **NIH NIH DP2** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $1,476,000

## Abstract

Project Summary
Normal nervous system function depends on proper communications between neurons and non-neuronal cells.
In the human brain, the majority of non-neuronal cells are called glia that consist of nearly half of total brain cells.
Despite decades of work focusing on neurons and glia alone, how they communicate with each other remains
poorly understood. This is partly due to a dearth of methods to comprehensively profile molecules that are
enriched at the neuron-glial interface during dynamic cell-cell interactions. This proposal aims to develop a
genetically-guided proteomic toolbox to spatiotemporally profile critical molecules enriched at neuron-glial
interface in vivo, allowing for molecular and genetic dissection of neuron-glial interactions. We will first design
and generate glial-specific cell surface proximity-labeling probes with the spatiotemporal precision. We will apply
this platform in the oligodendrocytes, the sole myelin-producing cells in the central nervous system (CNS), to
determine the molecular mechanisms governing the initiation of oligodendrocyte-axon ensheathment. We will
leverage this new method, along with single-cell RNA sequencing, genome-wide CRISPR screens, and novel
transgenic mouse strains, to interrogate a mysterious cell stage (the pre-myelinating oligodendrocytes) during
developmental and adaptive myelination. To extend the glial surface proximity labeling toolkit, we will develop a
neuron-glial complementary proximity labeling system allowing for visualization of transient neuron-glial
interactions and capture of molecules only enriched at neuron-glial interface in vivo. Using this system we will
address the molecular codes governing myelination selectivity between subsets of oligodendrocytes and
functionally distinct neuronal subpopulations. This proposed work will fulfill the knowledge gap in myelin biology,
and will have broader implications in understanding neuron-glial and glia-glial interaction mechanisms in general.
The methods and reagents established by the work will also greatly enrich the methods in studying diverse cell-
cell communications, including neuro-immune and cancer-immune interactions.

## Key facts

- **NIH application ID:** 10242478
- **Project number:** 1DP2MH129988-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Lu Sun
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,476,000
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242478

## Citation

> US National Institutes of Health, RePORTER application 10242478, Molecular and genetic decoding of neuron-glial interactions (1DP2MH129988-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242478. Licensed CC0.

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