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let‐7 regulates radial migration of new‐born neurons through positive regulation of autophagy
Author(s) -
Petri Rebecca,
Pircs Karolina,
Jönsson Marie E,
Åkerblom Malin,
Brattås Per Ludvik,
Klussendorf Thies,
Jakobsson Johan
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695235
Subject(s) - biology , neurogenesis , autophagy , neuroblast , microbiology and biotechnology , gene knockdown , olfactory bulb , tfeb , phenotype , rna , neuronal migration , neuroscience , genetics , gene , central nervous system , apoptosis
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 micro RNA (mi RNA ) let‐7 regulates radial migration by modulating autophagy in new‐born neurons. Using Argonaute2 immunoprecipitation, we performed global profiling of mi RNA s in adult‐born OB neurons and identified let‐7 as a highly abundant mi RNA 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 mi RNA ‐dependent link between autophagy and adult neurogenesis with implications for neurodegenerative diseases where these processes are impaired.