let-7 regulates radial migration of new-born neurons through positive regulation of autophagy

Rebecca Petri, Karolina Pircs, Marie E Jönsson, Malin Åkerblom, Per Ludvik Brattås, Thies Klussendorf, Johan Jakobsson

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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.

Original languageEnglish
Pages (from-to)1379-1391
JournalEMBO Journal
Volume36
Early online date2017 Mar 23
DOIs
Publication statusPublished - 2017

Subject classification (UKÄ)

  • Neurosciences

Free keywords

  • Journal Article

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