Temporal single-cell transcriptomic analysis of thesox1a:eGFPtransgenic line identified the lateral floor plate progenitor cells as the origin of intraspinal serotonergic neurons

Abstract

AbstractThe Sox family of transcription factors plays a crucial role in the development of the vertebrate nervous system. In the zebrafish embryo,sox1genes are expressed in neural progenitor cells and neurons of the ventral spinal cord. We recently reported that the loss of function ofsox1aandsox1bleads to a significant decline in a subtype of V2 neurons, called V2s, in zebrafish. Here, a single-cell RNA sequencing approach was used to analyse the transcriptome ofsox1alineage progenitors and neurons in the zebrafish spinal cord at four different time points during the first five days of embryonic development, using the Tg(sox1a:eGFP) line. In addition to the previously describedsox1a-expressing neurons, we found thatsox1ais also expressed in late-developing intraspinal serotonergic neurons (ISNs). Analysis of developmental trajectories from single-cell data and depletion of lateral floor plate (LFP) cells bynkx2.9morpholino knockdown suggest that ISNs arise from LFP precursor cells. Pharmacological inhibition of the Notch signalling pathway indicates that this pathway is required for the negative regulation of the development of LFP progenitor cells into ISN populations. Our results show that the zebrafish LFP is a precursor domain that longitudinally gives rise to ISNs in addition to the previously described KA” and V3 interneurons.