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Published on: February 17, 2016
Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating the Shh
Kayt Scott1, Rebecca O'Rourke1, Austin Gillen2,3
1Department of Pediatrics, Section of Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado 40045, USA.
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 whether 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 fewer 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 the allocation of oligodendrocyte lineage cell fates.This article has an associated 'The people behind the papers' interview.
Insights
Prdm8 controls spinal cord cell production by regulating the switch from motor neurons to oligodendrocyte precursor cells (OPCs). Loss of Prdm8 leads to fewer motor neurons and more oligodendrocytes due to elevated Shh signaling.
Area of Science:
- Developmental neurobiology
- Cell fate determination
- Transcriptional regulation
Background:
- Spinal cord progenitor cells (pMN) generate motor neurons and oligodendrocyte precursor cells (OPCs).
- The precise mechanisms governing the switch in pMN progenitor fate remain unclear.
- Prdm8, a transcriptional repressor, is expressed during these critical developmental periods.
Purpose of the Study:
- To investigate the role of Prdm8 in controlling pMN progenitor cell fate specification.
- To understand how Prdm8 regulates the transition from motor neuron to OPC production.
- To elucidate the relationship between Prdm8, Shh signaling, and oligodendrocyte lineage allocation.
Main Methods:
- Utilized zebrafish as a model organism for genetic analysis.
- Generated and analyzed prdm8 mutant zebrafish embryos and larvae.
- Investigated Shh signaling pathway activity in pMN progenitors.
Main Results:
- prdm8 mutant embryos exhibited a reduction in motor neurons, indicating an early switch to OPC production.
- prdm8 mutant larvae showed an increase in oligodendrocytes and a decrease in OPCs.
- Elevated Shh signaling was observed in pMN cells of mutant embryos during the switch.
- Inhibition of Shh signaling partially rescued motor neuron numbers but not oligodendrocyte proportions.
Conclusions:
- Prdm8 is crucial for regulating the timing of the motor neuron to OPC switch in pMN progenitors.
- Prdm8 influences the motor neuron-OPC transition by modulating Shh signaling levels.
- Prdm8 also plays a role in determining the subsequent fates within the oligodendrocyte lineage.
