let-7 regulates radial migration of new-born neurons through positive regulation of autophagy.
EMBO J
; 36(10): 1379-1391, 2017 05 15.
Article
em En
| MEDLINE
| ID: mdl-28336683
ABSTRACT
During adult neurogenesis, newly formed olfactory bulb (OB) interneurons migrate radially to integrate into specific layers of the OB Despite the importance of this process, the intracellular mechanisms that regulate radial migration remain poorly understood. Here, we find that microRNA (miRNA) let-7 regulates radial migration by modulating autophagy in new-born neurons. Using Argonaute2 immunoprecipitation, we performed global profiling of miRNAs in adult-born OB neurons and identified let-7 as a highly abundant miRNA family. Knockdown of let-7 in migrating neuroblasts prevented radial migration and led to an immature morphology of newly formed interneurons. This phenotype was accompanied by a decrease in autophagic activity. Overexpression of Beclin-1 or TFEB in new-born neurons lacking let-7 resulted in re-activation of autophagy and restored radial migration. Thus, these results reveal a miRNA-dependent link between autophagy and adult neurogenesis with implications for neurodegenerative diseases where these processes are impaired.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Movimento Celular
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MicroRNAs
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Suécia