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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. Haar, Lars Michels, Nicky C. H. van Kronenburg, Christiaan Meer, Jørgen Kjems, Vamshidhar R. Vangoor and R. Jeroen Pasterkamp ()
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Mateja Rybiczka-Tešulov: University Medical Center Utrecht, Utrecht University
Oxana Garritsen: University Medical Center Utrecht, Utrecht University
Morten T. Venø: Interdisciplinary Nanoscience Centre, Aarhus University
Laura Wieg: University Medical Center Utrecht, Utrecht University
Roland van Dijk: University Medical Center Utrecht, Utrecht University
Karim Rahimi: Interdisciplinary Nanoscience Centre, Aarhus University
Andreia Gomes-Duarte: University Medical Center Utrecht, Utrecht University
Marina de Wit: University Medical Center Utrecht, Utrecht University
Lieke L. Haar: University Medical Center Utrecht, Utrecht University
Lars Michels: University Medical Center Utrecht, Utrecht University
Nicky C. H. van Kronenburg: University Medical Center Utrecht, Utrecht University
Christiaan Meer: University Medical Center Utrecht, Utrecht University
Jørgen Kjems: Interdisciplinary Nanoscience Centre, Aarhus University
Vamshidhar R. Vangoor: University Medical Center Utrecht, Utrecht University
R. Jeroen Pasterkamp: University Medical Center Utrecht, Utrecht University

Nature Communications, 2024, vol. 15, issue 1, 1-23

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51041-1

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