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
  • Animals
  • Cell Differentiation*
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism*
  • Histone Methyltransferases/genetics
  • Histone Methyltransferases/metabolism*
  • Mice
  • Mice, Transgenic
  • Motor Neurons/cytology
  • Motor Neurons/metabolism*
  • Neural Stem Cells/cytology
  • Neural Stem Cells/metabolism*
  • Oligodendroglia/cytology
  • Oligodendroglia/metabolism*
  • Signal Transduction*
PubMed
32680935 Full text @ Development
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
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes