||The goal of this study was to identify distinct cell populations that arise from ventral spinal cord pMN progenitors. To do so, we sorted fluorescently marked pMN cells obtained from Tg(olig2:EGFP) zebrafish embryos at 24, 36 and 48 hours post fertilization and performed 10X Chromium single cell RNA-seq.
||sonic hedgehog; motor neurons; oligodendrocytes; pmn progenitors; spinal cord; zebrafish; ventral spinal-cord; sonic-hedgehog; transcription factor; morphogen gradient; expression; differentiation; lineage; cells; olig2; promotes
||Scott K, O'Rourke R, Gillen A, Appel B. Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating the Shh signaling response. Development 2020 Aug 27;147(16). PMID: 32680935
||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. HowpMNprogenitors switch fromproducingmotor 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 systemto 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.