Insights into the mechanisms of neuron generation and specification in the zebrafish ventral spinal cord.

The vertebrate nervous system is composed of a wide range of neurons and complex synaptic connections, raising the intriguing question of how neuronal diversity is generated. The spinal cord provides an excellent model for exploring the mechanisms governing neuronal diversity due to its simple neural network and the conserved molecular processes involved in neuron formation and specification during evolution. This review specifically examines two distinct progenitor domains present in the zebrafish ventral spinal cord: the lateral floor plate (LFP) and the p2 progenitor domain. The LFP is responsible for the production of GABAergic Kolmer-Agduhr neurons (KA″), glutamatergic V3 neurons, and intraspinal serotonergic neurons, while the p2 domain generates V2 precursors that subsequently differentiate into three unique subpopulations of V2 neurons, namely glutamatergic V2a, GABAergic V2b, and glycinergic V2s. Based on recent findings, we will examine the fundamental signaling pathways and transcription factors that play a key role in the specification of these diverse neurons and neuronal subtypes derived from the LFP and p2 progenitor domains.

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

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.