PUBLICATION
Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating Shh signaling response
- Authors
- Scott, K., O'Rourke, R., Gillen, A., Appel, B.
- ID
- ZDB-PUB-200719-15
- Date
- 2020
- Source
- Development (Cambridge, England) 147(16): (Journal)
- Registered Authors
- Appel, Bruce
- Keywords
- Motor neurons, Oligodendrocytes, Sonic hedgehog, Spinal cord, Zebrafish, pMN progenitors
- Datasets
- GEO:GSE155988
- MeSH Terms
-
- Mice, Transgenic
- Signal Transduction*
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism*
- Histone Methyltransferases/genetics
- Histone Methyltransferases/metabolism*
- Animals
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Mice
- Cell Differentiation*
- Motor Neurons/cytology
- Motor Neurons/metabolism*
- Oligodendroglia/cytology
- Oligodendroglia/metabolism*
- Neural Stem Cells/cytology
- Neural Stem Cells/metabolism*
- PubMed
- 32680935 Full text @ Development
Citation
Scott, K., O'Rourke, R., Gillen, A., Appel, B. (2020) Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating Shh signaling response. Development (Cambridge, England). 147(16):.
Abstract
Spinal cord pMN progenitors sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Some OPCs differentiate rapidly as myelinating oligodendrocytes whereas others remain into adulthood. How pMN progenitors switch from producing motor neurons to OPCs with distinct fates is poorly understood. pMN progenitors express prdm8, which encodes a transcriptional repressor, during motor neuron and OPC formation. To determine if prdm8 controls pMN cell fate specification, we used zebrafish as a model system to investigate prdm8 function. Our analysis revealed that prdm8 mutant embryos have a deficit of motor neurons resulting from a premature switch from motor neuron to OPC production. Additionally, prdm8 mutant larvae have excess oligodendrocytes and a concomitant deficit of OPCs. Notably, pMN cells of mutant embryos have elevated Shh signaling coincident with the motor neuron to OPC switch. Inhibition of Shh signaling restored the number of motor neurons to normal but did not rescue the proportion of oligodendrocytes. These data suggest that Prdm8 regulates the motor neuron-OPC switch by controlling the level of Shh activity in pMN progenitors and also regulates allocation of oligodendrocyte lineage cell fates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping