title: Convergent repression of Foxp2 3'UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons.
abstract: MicroRNAs (miRNAs) are rapidly emerging as a new layer of regulation of mammalian brain development. However, most of the miRNA target genes remain unidentified. Here, we explore gene expression profiling upon miRNA depletion and in vivo target validation as a strategy to identify novel miRNA targets in embryonic mouse neocortex. By this means, we find that Foxp2, a transcription factor associated with speech and language development and evolution, is a novel miRNA target. In particular, we find that miR-9 and miR-132 are able to repress ectopic expression of Foxp2 protein by targeting its 3' untranslated region (3'UTR) in vivo. Interestingly, ectopic expression of Foxp2 in cortical projection neurons (a scenario that mimics the absence of miRNA-mediated silencing of Foxp2 expression) delays neurite outgrowth in vitro and impairs their radial migration in embryonic mouse neocortex in vivo. Our results uncover a new layer of control of Foxp2 expression that may be required for proper neuronal maturation.
authors.affiliation: Department of Neuroscience and Brain Technologies, Fondazione Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova, Italy.
authors.forename: Yoanne M
authors.initials: YM
authors.lastname: Clovis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Enard
authors.forename: Federica
authors.initials: F
authors.lastname: Marinaro
authors.forename: Wieland B
authors.initials: WB
authors.lastname: Huttner
authors.forename: Davide
authors.initials: D
authors.lastname: De Pietri Tonelli
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019579:Neocortex / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; C546976:MIRN132 microRNA, mouse; C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; D012097:Repressor Proteins