Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development

Mateja Rybiczka-Tešulov, Oxana Garritsen, Morten T. Venø, Laura Wieg, Roland van Dijk, Karim Rahimi, Andreia Gomes-Duarte, Marina de Wit, Lieke L. van de Haar, Lars Michels, Nicky C.H. van Kronenburg, Christiaan van der Meer, Jørgen Kjems, Vamshidhar R. Vangoor, R. Jeroen Pasterkamp*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 non-coding RNAs (ncRNAs), remain incompletely understood. Here, we establish the transcriptomic landscape and alternative splicing patterns of circular RNAs (circRNAs) at key developmental timepoints in mouse mDA neurons in vivo using fluorescence-activated cell sorting followed by short- and long-read RNA sequencing. In situ hybridisation shows expression of several circRNAs during early mDA neuron development and post-transcriptional silencing unveils roles for different circRNAs in regulating mDA neuron morphology. Finally, in utero electroporation and time-lapse imaging implicate circRmst, a circRNA with widespread morphological effects, in the migration of developing mDA neurons in vivo. Together, these data for the first time suggest a functional role for circRNAs in developing mDA neurons and characterise poorly defined aspects of mDA neuron development.

Original languageEnglish
Article number6773
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 8 Aug 2024

Cite this