TY - JOUR
T1 - Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development
AU - Rybiczka-Tešulov, Mateja
AU - Garritsen, Oxana
AU - Venø, Morten T.
AU - Wieg, Laura
AU - Dijk, Roland van
AU - Rahimi, Karim
AU - Gomes-Duarte, Andreia
AU - Wit, Marina de
AU - van de Haar, Lieke L.
AU - Michels, Lars
AU - van Kronenburg, Nicky C.H.
AU - van der Meer, Christiaan
AU - Kjems, Jørgen
AU - Vangoor, Vamshidhar R.
AU - Pasterkamp, R. Jeroen
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/8/8
Y1 - 2024/8/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85200857432&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-51041-1
DO - 10.1038/s41467-024-51041-1
M3 - Article
C2 - 39117691
AN - SCOPUS:85200857432
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6773
ER -