Transcriptomic profiling of long non-coding RNAs identifies circRmst as a regulator of midbrain dopamine neuron migration [time series]

Midbrain dopamine (mDA) neurons play an essential role in cognitive and motor behaviours and are linked to different brain disorders. However, the molecular mechanisms underlying their development, and in particular the role of long non-coding RNAs (lncRNAs), remain incompletely understood. Here, we establish the transcriptomic landscape and alternative splicing patterns of linear and circular ncRNAs (lncRNAs and circRNAs) at key developmental timepoints in mouse mDA neurons using RNAseq at different time points during early development. Spatial analysis shows strong and subregion-specific expression of circRmst in mDA neurons and its post-transcriptional silencing affects soma size, TH+ neuron number, and mDA neuron positioning. Time-laps imaging indeed reveals that circRmst inhibits migration speed in developing mDA neurons. Together, these data for the first time establish a functional role for circRNAs in mDA neurons, further characterize poorly defined aspects of mDA neuron development, and provide a unique framework for future interrogation of lncRNAs in developing mDA neurons.