PUBLICATION
Gsx2 Regulates Oligodendrocyte Precursor Formation in the Zebrafish Spinal Cord
- Authors
- Arena, K.A., Kearns, C.A., Ahmed, M., O'Rourke, R., Sagerström, C.G., Franco, S.J., Appel, B.
- ID
- ZDB-PUB-260107-6
- Date
- 2026
- Source
- Developmental Biology 531: 30-44 (Journal)
- Registered Authors
- Appel, Bruce, Kearns, Christina, Sagerström, Charles
- Keywords
- none
- Datasets
- GEO:GSE316142
- MeSH Terms
-
- Animals
- CRISPR-Cas Systems
- Cell Differentiation/genetics
- Cell Lineage
- Gene Expression Regulation, Developmental
- Gene Regulatory Networks
- Homeodomain Proteins*/genetics
- Homeodomain Proteins*/metabolism
- Neural Stem Cells/cytology
- Neural Stem Cells/metabolism
- Oligodendrocyte Precursor Cells*/cytology
- Oligodendrocyte Precursor Cells*/metabolism
- Oligodendroglia*/cytology
- Oligodendroglia*/metabolism
- Spinal Cord*/cytology
- Spinal Cord*/embryology
- Spinal Cord*/metabolism
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41491310 Full text @ Dev. Biol.
Citation
Arena, K.A., Kearns, C.A., Ahmed, M., O'Rourke, R., Sagerström, C.G., Franco, S.J., Appel, B. (2026) Gsx2 Regulates Oligodendrocyte Precursor Formation in the Zebrafish Spinal Cord. Developmental Biology. 531:30-44.
Abstract
Nervous system development relies on sequential and coordinated formation of diverse neurons and glia from neural progenitor cells (NPCs). In the spinal cord, NPCs of the pMN domain produce neurons early in development followed by oligodendrocyte precursor cells (OPCs), which subsequently differentiate as oligodendrocytes (OLs), the myelinating glia of the central nervous system. The mechanisms that specify neural progenitor cells to the OL lineage are not yet well understood. Using zebrafish as an experimental model system, we generated single-cell RNA sequencing and single-nuclei ATAC sequencing data that identified a subpopulation of NPCs, called pre-OPCs, that appeared fated to produce OPCs. pre-OPCs uniquely express several genes that encode transcription factors specific to the OL lineage, including Gsx2, which regulates OPC formation in the mouse forebrain. To investigate Gsx2 function in zebrafish OPC specification, we used CRISPR/Cas9 genome editing to create gsx2 loss-of-function alleles. gsx2 homozygous mutant embryos initiated OPC formation prematurely and produced excess OPCs without altering OL differentiation. Using our single-nuclei multi-omics dataset, we predicted a gene regulatory network centered around gsx2 and identified genes that might be transcriptionally regulated by Gsx2. Taken together, our studies suggest that Gsx2 expression in pre-OPCs contributes to the timing of OPC specification.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping