# Mechanisms of CNS myelin targeting

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $500,200

## Abstract

Project Abstract:
Efficient vertebrate nervous systems require the precise insulation of central nervous system (CNS) axons by
myelinating oligodendrocytes. However, we know very little about how axons are selected for myelination and
why some CNS structures are avoided. We set out to investigate these questions and identified several genes,
including junction adhesion molecules 2&3 (jams 2&3) and transmembrane protein 125b (tmem125b) as putative
regulators of CNS myelin targeting and growth. Tmem125b is expressed in mature, myelinating oligodendrocytes
in zebrafish, mice, and humans with an expression pattern that is consistent with its possible role in myelin
targeting and myelin maintenance and jams 2&3 are expressed in neurons and oligodendrocyte lineage cells. In
our preliminary studies, we have discovered that mutations of tmem125b as well as jams 2&3 cause ectopic
myelination of CNS neuronal soma, consistent with a role for these proteins in myelin targeting and/or growth.
In this application, we will extend these findings to: 1) determine the role of tmem125b in CNS myelination (Aim
1), 2) characterize the role of jams 2&3 in developmental myelination (Aim 2), and 3) identify the binding partners
for Tmem125b that inhibit ectopic myelination to neuronal soma (Aim 3). When complete, we will have a deeper
understanding of the role of tmem125b and jams 2&3 in CNS myelination as well as insight into the mechanisms
that drive appropriate myelin targeting during development.

## Key facts

- **NIH application ID:** 10980711
- **Project number:** 1R01NS134768-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Sarah C Kucenas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $500,200
- **Award type:** 1
- **Project period:** 2024-07-06 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980711

## Citation

> US National Institutes of Health, RePORTER application 10980711, Mechanisms of CNS myelin targeting (1R01NS134768-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10980711. Licensed CC0.

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