Expression of myelin transcription factor 1 and lamin B receptor mediate neural progenitor fate transition in the zebrafish spinal cord pMN domain

The pMN domain is a restricted domain in the ventral spinal cord, defined by the expression of the olig2 gene. Though it is known that the pMN progenitor cells can sequentially generate motor neurons and oligodendrocytes, the lineages of these progenitors are controversial and how their progeny are generated is not well understood. Using single-cell RNA sequencing, here, we identified a previously unknown hetero-geneity among pMN progenitors with distinct fates and molecular signatures in zebrafish. Notably, we characterized two distinct motor neuron lineages using bioinformatic analysis. We then went on to investigate specific molecular programs that regulate neural progenitor fate transition. We validated experimentally that expression of the transcription factor myt1 (myelin transcription factor 1) and inner nuclear membrane integral proteins lbr (lamin B receptor) were critical for the development of motor neurons and neural progenitor maintenance, respectively. We anticipate that the transcriptome features and molecular programs identified in zebrafish pMN progenitors will not only provide an in-depth understanding of previous findings regarding the lineage analysis of oligoden-drocyte progenitor cells and motor neurons but will also help in further understanding of the molecular programming involved in neural progenitor fate transition.

Automated summary

Using single-cell RNA sequencing, this study reveals the heterogeneity of pMN progenitors in zebrafish, with distinct fates and molecular signatures. Two different motor neuron lineages are characterized, and the critical roles of myt1 and lbr in neural progenitor fate transition are validated.