How gene expression temporally unfolds and is regulated to shape post-
differentiation development of neuronal identity is poorly understood. Here, RNA-
sequencing of flow sorted serotonin (5-HT) neurons uncovers multiple discrete
gene expression trajectories during 5-HT neuron maturation. Integration of ChIP-
seq and RNA-seq datasets shows that transcription factor, Pet-1/FEV, regulates
trajectories of diverse targets including a transcription factor network and pan-
neuronal and neuron-type identity features. The profound disruption of
expression patterns in Pet-1-/- 5-HT neurons permanently stalled maturation of
their active and passive membrane characteristics. Collapse of specific
trajectories blocked acquisition of glutamatergic and G-protein coupled receptor-
signaling pathways required for mature afferent responses of 5-HT neurons.
Moreover, continuous transcriptional activity was required to shape trajectories of
key identity features defining mature 5-HT neurons. Our findings identify a
transcriptional program that promotes maturation of serotonergic efferent and
afferent connectivity and provides a framework for understanding how immature
serotonergic activity may contribute to psychiatric disorders. Less...