# Prdm8 inhibits oligodendrocyte differentiation through gene repression

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2020 · $26,653

## Abstract

Project Summary: Oligodendrocytes (OLs) are vital for nervous system function by myelinating axons in the
central nervous system (CNS) to increase conduction velocity and provide metabolic support. The majority of
OLs are generated by ventral pMN progenitors defined by the expression of the basic helix loop helix (bhlh)
transcription factor Oligodendrocyte Transcription Factor 2 (Olig2), which give rise to motor neurons and OLs
sequentially. OLs are initially specified as oligodendrocyte precursor cells (OPCs), which migrate through the
spinal cord and then differentiate. However, not all OPCs become myelinating OLs. Instead, many remain as
fate restricted proliferative progenitors through adulthood. Though 5-8% of the cells in the adult CNS are OPCs,
the mechanisms that preserve this population are not well understood. As OPCs undergo differentiation, genes
that promote cell cycle progression and progenitor identity are downregulated, while genes required for
myelination and oligodendrocyte differentiation are upregulated. These changes in gene expression are
orchestrated by stage-specific transcriptional activity of core oligodendrocyte lineage transcription factors such
as Olig2. Olig2 can be a transcriptional repressor or activator depending on interactions with different co-factors.
For example, Olig2 forms a complex with SWI/SNF Related, Matrix Associated, Actin Dependent (SMARCA4/
Brg1) to directly activate expression of myelin genes. Though Olig2 is expressed in all OL lineage cells, it is not
well understood what regulates the transcriptional activity of Olig2 in OPCs. RNA-Seq data collected in the Appel
lab found that PR/SET domain 8 (prdm8), a gene that encodes a transcriptional repressor, is expressed by OPCs
but not oligodendrocytes. In the CNS, Prdm8 acts as a repressive co-factor with a close relative of Olig2, Basic
Helix-Loop-Helix Domain Containing, Class B, 5 (Bhlhb5). Loss of function prdm8 zebrafish larvae have more
oligodendrocytes and fewer OPCs, suggesting that Prdm8 inhibits oligodendrocyte differentiation. Using a
combination of genetic manipulations, microscopy and biochemical methods in vivo, this proposal will address
the possibility that Prdm8 forms a complex with Olig2 to maintain OPCs by repressing genes required for
oligodendrocyte differentiation. Aim 1 will test the sufficiency of Prdm8 to the inhibit oligodendrocyte fate and
myelination. Aim 2 addresses genetic targets of Prdm8 in the oligodendrocyte lineage. Aim 3 will evaluate Prdm8
and Olig2 interactions. These investigations will advance the field of oligodendrocyte biology by providing a
deeper understanding of transcriptional regulation that preserves OPCs.

## Key facts

- **NIH application ID:** 10139906
- **Project number:** 1F31NS116922-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kathryn F Scott
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $26,653
- **Award type:** 1
- **Project period:** 2020-12-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10139906

## Citation

> US National Institutes of Health, RePORTER application 10139906, Prdm8 inhibits oligodendrocyte differentiation through gene repression (1F31NS116922-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10139906. Licensed CC0.

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