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

Petri, Rebecca LU ; Pircs, Karolina LU orcid ; Jönsson, Marie E LU ; Åkerblom, Malin LU ; Brattås, Per Ludvik LU ; Klussendorf, Thies LU and Jakobsson, Johan LU orcid (2017) In EMBO Journal 36. p.1379-1391
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.... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Journal Article
in
EMBO Journal
volume
36
pages
1379 - 1391
publisher
Oxford University Press
external identifiers
  • scopus:85016225503
  • wos:000401226700007
  • pmid:28336683
ISSN
1460-2075
DOI
10.15252/embj.201695235
language
English
LU publication?
yes
id
8fd362f6-fa5f-4a27-a2dd-2bb188f30645
date added to LUP
2017-03-27 13:56:43
date last changed
2025-01-07 10:20:20
@article{8fd362f6-fa5f-4a27-a2dd-2bb188f30645,
  abstract     = {{<p>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.</p>}},
  author       = {{Petri, Rebecca and Pircs, Karolina and Jönsson, Marie E and Åkerblom, Malin and Brattås, Per Ludvik and Klussendorf, Thies and Jakobsson, Johan}},
  issn         = {{1460-2075}},
  keywords     = {{Journal Article}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{1379--1391}},
  publisher    = {{Oxford University Press}},
  series       = {{EMBO Journal}},
  title        = {{let-7 regulates radial migration of new-born neurons through positive regulation of autophagy}},
  url          = {{https://lup.lub.lu.se/search/files/23131188/EMBOJ_2016_95235R.pdf}},
  doi          = {{10.15252/embj.201695235}},
  volume       = {{36}},
  year         = {{2017}},
}