Emergence of neuronal diversity during vertebrate brain development

Abstract

Neurogenesis in the vertebrate brain comprises many steps ranging from the proliferation of progenitors to the differentiation and maturation of neurons. Although these processes are highly regulated, the landscape of transcriptional changes and progenitor identities underlying brain development are poorly characterized. Here, we describe the first developmental single-cell RNAseq catalog of more than 200,000 zebrafish brain cells encompassing 12 stages from 12 hours post-fertilization to 15 days post-fertilization. We characterize known and novel gene markers for more than 800 clusters across these timepoints. Our results capture the temporal dynamics of multiple neurogenic waves from embryo to larva that expand neuronal diversity from ~20 cell types at 12 hpf to ~100 cell types at 15 dpf. We find that most embryonic neural progenitor states are transient and transcriptionally distinct from long-lasting neural progenitors of post-embryonic stages. Furthermore, we reconstruct cell specification trajectories for the retina and hypothalamus, and identify gene expression cascades and novel markers. Our analysis reveal that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo, while hypothalamic neural progenitors become progressively distinct with developmental time. These data provide the first comprehensive single-cell transcriptomic time course for vertebrate brain development and suggest distinct neurogenic regulatory paradigms between different stages and tissues.

The conserved wobble uridine tRNA thiolase Ctu1 is required to sustain development and differentiation

“…This suggests that the deletion of CTU1 may affect the formation and guidance of the growth cone. Affected, which in turn affects the growth and connection of neuronal axons [65] . This eventually leads to abnormal development of the nervous system, including errors in neuronal connections, errors in axon path selection, or defects in the formation of neural circuits [66] .In light of the intricate nature of neural development, additional research and a greater amount of experimental evidence are still required.…”