Fate transitions in Drosophila neural lineages: a single cell road map to mature neurons

Autor: Nikolaos Konstantinides, Teles-Reis J, Homem Ccf, Patrícia H. Brito, Marques Gs
Rok vydání: 2021
Předmět:
DOI: 10.1101/2021.06.22.449317
Popis: Brain development requires the formation of thousands of neurons and glia and their coordinated maturation to ensure correct circuit formation. Neuronal fate is determined by several layers of gene regulatory networks during neuronal lineage progression. Once specified, neurons must still undergo a critical maturation period, involving the stepwise expression of functional feature genes such as cell surface molecules, ion channels or neurotransmitter receptors. The precise mechanisms that govern neuronal maturation remain however poorly understood. Here, we use single-cell RNA sequencing combined with a conditional genetic strategy to select and analyse neural lineages and their young progeny at a restrictive timepoint to investigate the transcriptional trajectories in young developing secondary neurons in the Drosophila larval brain. Our findings reveal that neuron maturation starts very quickly after neuronal birth, and sub-divide the process of maturation into 3 distinct phases: Phase 1 is composed by immature neurons that have yet to start expressing mRNA of mature neuronal features; Phase 2 includes neurons that start transcribing but not translating maturation markers such as neurotransmitter genes; Phase 3 neurons start translating mature neuronal features, in a coordinated fashion with the animal developmental stage. This dataset represents a complete transcriptomic characterization of the neural lineages generated at this larval stage in the central brain and ventral nerve cord. Its analysis has also allowed for the characterization of a yet undefined transitional state, the immature ganglion mother cells, and has proven useful for the identification of known and novel fate regulators.
Databáze: OpenAIRE