# Genetic approaches to address oligodendrocyte progenitor cell diversity

> **NIH NIH R21** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $238,500

## Abstract

Abstract
Oligodendrogenesis is a complex process that requires changes in transcription factor expression for the
generation, expansion, and differentiation of oligodendrocyte progenitor cells (OPCs) into mature
oligodendrocytes (OLs) that produce myelin. The overall goal of this proposal is to focus on understanding the
diversity of the OPC stage in the process. Our gene expression screen to identity novel OPC markers revealed
the homeobox gene Gsx1 exhibits temporal expression in OPCs during development. Here we propose to
develop new mouse models to address the role of Gsx1 in OPC biology. In the first aim, we will test if Gsx1 is a
stage specific regulator in OPCs and generate an OPC specific conditional mutant to determine if altering Gsx1
gene function causes changes in OPC expansion, OL differentiation, and/or myelination. We will also test if the
closely related gene, Gsx2, compensates for the loss of Gsx1 in OPCs. In the second aim, we will test if sustained
Gsx1 expression throughout OL development promotes OPC generation and subsequently OL differentiation
and myelination using a temporally controlled doxycycline regulated gain-of-function model. In the third aim, we
will utilize the Gsx1 lineage to reveal OPC diversity during postnatal oligodendrogenesis by generating a novel
Gsx1 reporter allele using Timer Fluorescent Protein. These studies will identify the specific roles of Gsx1 during
the OPC stage of OL development and provide new mouse models key for understanding the complex regulation
of OPCs during oligodendrogenesis.

## Key facts

- **NIH application ID:** 10454507
- **Project number:** 1R21NS123974-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** RONALD R WACLAW
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $238,500
- **Award type:** 1
- **Project period:** 2022-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454507

## Citation

> US National Institutes of Health, RePORTER application 10454507, Genetic approaches to address oligodendrocyte progenitor cell diversity (1R21NS123974-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10454507. Licensed CC0.

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