# Characterizing the role of migration, proliferation, and contact-mediated repulsion in oligodendrocyte progenitor cell tiling

> **NIH NIH F31** · UNIVERSITY OF VIRGINIA · 2020 · $34,940

## Abstract

Project Summary
Myelination of axons in the central nervous system (CNS) is required for the propagation of electrical activity in
neurons and maintenance of axonal health. Oligodendrocyte progenitor cells (OPCs) give rise to the myelinating
cells of the CNS, known as oligodendrocytes. While the majority of OPCs differentiate into oligodendrocytes, a
population of OPCs remains undifferentiated and evenly distributed in the CNS throughout life. How OPCs space
during development and maintain their spacing into adulthood is unknown. In vivo imaging in adult mouse cortex
and the spinal cord of zebrafish larvae demonstrate that OPCs undergo a process termed tiling. We define tiling
as the dynamic process that OPCs undergo during development where they establish and maintain even spacing
and distinct territories that, under non-pathological conditions, do not overlap. During tiling, OPCs also exhibit
contact-mediated repulsion (CMR). CMR is a process whereby migrating OPCs will retract their processes and
change their migratory direction following contact with other OPCs. However, the molecular mechanisms that
OPCs use to facilitate tiling and CMR are unknown. Additionally, demyelinating diseases cause increased OPC
clustering, which signifies a disruption in local tiling mechanisms. Understanding the fundamental mechanisms
of that regulate OPC-OPC interactions will provide insight into the developmental processes of OPC tiling and
potential targets for modulating OPC migration and recruitment to demyelinated lesions. The purpose of this
proposal is to elucidate the mechanisms that facilitate the rapid tiling of OPCs during development by
investigating three important processes during tiling: (1) OPC proliferation, (2) OPC migration, and (3)
OPC CMR. To investigate OPC tiling during development, I will use zebrafish (Danio rerio) as a vertebrate model
system. The relative simplicity of this system and clarity of the spinal cord of zebrafish embryos and larvae allow
for visualization of OPC migration, proliferation, and CMR in a large portion of the developing CNS. I will use a
candidate gene approach based on previous literature to identify potential mediators of proliferation and CMR.
Additionally, I will investigate candidates identified from an unbiased small molecule screen to identify novel
mediators of OPC migration during developmental tiling. I will then use a combination of CRISPR/Cas9 gene
editing techniques, pharmacological inhibitors, in vivo imaging, and immunohistochemistry to characterize the
role of OPC proliferation, migration, and CMR to developmental OPC tiling. Overall, this work will expand our
understanding of OPC tiling and interactions and potentially provide translational targets for demyelinating
diseases, such as multiple sclerosis.

## Key facts

- **NIH application ID:** 9925058
- **Project number:** 5F31NS108660-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Maria Ali
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,940
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925058

## Citation

> US National Institutes of Health, RePORTER application 9925058, Characterizing the role of migration, proliferation, and contact-mediated repulsion in oligodendrocyte progenitor cell tiling (5F31NS108660-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9925058. Licensed CC0.

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