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Nat Commun ; 15(1): 6773, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39117691

RESUMO

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.


Assuntos
Movimento Celular , Neurônios Dopaminérgicos , Regulação da Expressão Gênica no Desenvolvimento , Mesencéfalo , RNA Circular , Animais , RNA Circular/genética , RNA Circular/metabolismo , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/citologia , Mesencéfalo/metabolismo , Mesencéfalo/citologia , Mesencéfalo/embriologia , Camundongos , Movimento Celular/genética , Neurogênese/genética , Feminino , Processamento Alternativo , Camundongos Endogâmicos C57BL , Transcriptoma
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