Cell fate in the spinal cord: Prdm8 says ‘shh’ to Shh

During vertebrate development, pMN progenitors in the ventral spinal cord sequentially give rise to motor neurons and oligodendrocyte precursor cells (OPCs); OPCs in turn either differentiate or persist into adulthood. While Shh signalling is known to play an important role in pMN development, how it translates into altered cell fates is still incompletely understood. Now, Kayt Scott, a graduate student in Bruce Appel's lab, and her colleagues investigate the role of the transcriptional co-regulator Prdm8 in the zebrafish spinal cord. They first show that, as in the mouse, prdm8 is expressed in the pMN domain. Single cell sequencing indicates that prdm8 is expressed both by presumptive pMN progenitors and presumptive OPCs; prdm8 mRNA is progressively restricted to the OPC lineage over time and then downregulated as oligodendrocytes differentiate (it remains high in OPCs). prdm8 mutants display an excess of oligodendrocytes at the expense of OPCs, and also have fewer motor neurons due to pMN progenitors prematurely switching from producing motor neurons to OPCs (as shown by precocious expansion of nkx2.2a expression). prdm8 mutants have elevated levels of Shh signalling, independent of ligand expression, and finally, inhibition of Shh signalling rescues the deficit of motor neurons in prdm8 mutants, but cannot rescue the excess of oligodendrocytes. Thus, Prdm8 dampens Shh signalling in pMN progenitors to regulate the neural/glia switch, and also suppresses OPC differentiation.