sox1a:eGFP transgenic line and single-cell transcriptomics reveal the origin of zebrafish intraspinal serotonergic neurons

Fushun Chen; Melina Köhler; Gokhan Cucun; Masanari Takamiya; Caghan Kizil; Mehmet Ilyas Cosacak; Sepand Rastegar

doi:10.1016/j.isci.2023.107342

sox1a:eGFP transgenic line and single-cell transcriptomics reveal the origin of zebrafish intraspinal serotonergic neurons

iScience. 2023 Jul 11;26(8):107342. doi: 10.1016/j.isci.2023.107342. eCollection 2023 Aug 18.

Authors

Fushun Chen¹, Melina Köhler¹, Gokhan Cucun¹, Masanari Takamiya¹, Caghan Kizil^{2

3}, Mehmet Ilyas Cosacak², Sepand Rastegar¹

Affiliations

¹ Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Campus North, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
² German Center for Neurodegenerative Diseases (DZNE) Dresden, Helmholtz Association, Tatzberg 41, 01307 Dresden, Germany.
³ Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, 630 W 168th Street, New York, NY 10032, USA.

Abstract

Sox transcription factors are crucial for vertebrate nervous system development. In zebrafish embryo, sox1 genes are expressed in neural progenitor cells and neurons of ventral spinal cord. Our recent study revealed that the loss of sox1a and sox1b function results in a significant decline of V2 subtype neurons (V2s). Using single-cell RNA sequencing, we analyzed the transcriptome of sox1a lineage progenitors and neurons in the zebrafish spinal cord at four time points during embryonic development, employing the Tg(sox1a:eGFP) line. In addition to previously characterized sox1a-expressing neurons, we discovered the expression of sox1a in late-developing intraspinal serotonergic neurons (ISNs). Developmental trajectory analysis suggests that ISNs arise from lateral floor plate (LFP) progenitor cells. Pharmacological inhibition of the Notch signaling pathway revealed its role in negatively regulating LFP progenitor cell differentiation into ISNs. Our findings highlight the zebrafish LFP as a progenitor domain for ISNs, alongside known Kolmer-Agduhr (KA) and V3 interneurons.

Keywords: Cell biology; Neuroscience; Omics; Transcriptomics.