Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro.
Nat Commun
; 13(1): 5427, 2022 09 15.
Article
em En
| MEDLINE
| ID: mdl-36109497
ABSTRACT
Neurons born in the embryo can undergo a protracted period of maturation lasting well into postnatal life. How gene expression changes are regulated during maturation and whether they can be recapitulated in cultured neurons remains poorly understood. Here, we show that mouse motor neurons exhibit pervasive changes in gene expression and accessibility of associated regulatory regions from embryonic till juvenile age. While motifs of selector transcription factors, ISL1 and LHX3, are enriched in nascent regulatory regions, motifs of NFI factors, activity-dependent factors, and hormone receptors become more prominent in maturation-dependent enhancers. Notably, stem cell-derived motor neurons recapitulate ~40% of the maturation expression program in vitro, with neural activity playing only a modest role as a late-stage modulator. Thus, the genetic maturation program consists of a core hardwired subprogram that is correctly executed in vitro and an extrinsically-controlled subprogram that is dependent on the in vivo context of the maturing organism.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neurogênese
/
Neurônios Motores
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article