# Temporal and Spatial Control of Oligodendrocyte Fate Specification

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $561,370

## Abstract

PROJECT SUMMARY
The long-term goal of this project is to understand how oligodendrocytes, the myelinating glia cell type of the
vertebrate central nervous system, are formed during development. In the ventral spinal cord and dorsal
forebrain, neural progenitors first produce neurons followed by oligodendrocyte precursor cells (OPCs), which
migrate and divide to populate the neural tube. Subsequently, many OPCs stop dividing and differentiate as
myelinating oligodendrocytes. Whereas we know a considerable amount about the mechanisms that promote
oligodendrocyte differentiation and myelination, we know very little about mechanisms that regulate the very
earliest steps in specifying progenitors for oligodendrocyte fate. Based on our in vivo, live imaging-based fate
mapping studies, we discovered that different spinal cord and forebrain progenitor cells produce neurons and
OPCs. We have now used single cell RNA-seq analyses to identify a transcriptional state of these pre-OPC
progenitors, and have identified candidate cell-intrinsic programs and cell-extrinsic pathways that are conserved
between nervous system regions and across vertebrate species. Using zebrafish and mice as model systems,
this project will identify the molecular mechanisms that guide formation of OPCs from neural progenitors. Specific
Aim 1 will test a hypothesis that the pioneer transcription factor Ascl1 establishes the epigenetic and
transcriptional state of pre-OPCs. Aim 2 will investigate the mechanisms by which Notch signaling selects a
subset of neural progenitors for a pre-OPC fate. Specific Aim 3 will test a hypothesis that the transcription factor
Gsx2 helps specify a pre-OPC state and/or regulates a pre-OPC to OPC transition. The results of this project
have the potential for important new insights into developmental myelination, the causes of myelin disease and
potential strategies to restore myelin following disease and injury.

## Key facts

- **NIH application ID:** 10650855
- **Project number:** 5R01NS124166-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Bruce H Appel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $561,370
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10650855

## Citation

> US National Institutes of Health, RePORTER application 10650855, Temporal and Spatial Control of Oligodendrocyte Fate Specification (5R01NS124166-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10650855. Licensed CC0.

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