The microRNA miR-21 Is a Mediator of FGF8 Action on Cortical COUP-TFI Translation
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Authors
Terrigno, Marco
Bertacchi, Michele
Baumgart, Mario
Calvello, Mariantonietta
Cellerino, Alessandro
Studer, Michele
Cremisi, Federico
Publication Date
2018-09-11Journal Title
Stem Cell Reports
ISSN
2213-6711
Publisher
Elsevier
Volume
11
Issue
3
Pages
756-769
Type
Article
Metadata
Show full item recordCitation
Terrigno, M., Bertacchi, M., Pandolfini, L., Baumgart, M., Calvello, M., Cellerino, A., Studer, M., & et al. (2018). The microRNA miR-21 Is a Mediator of FGF8 Action on Cortical COUP-TFI Translation. Stem Cell Reports, 11 (3), 756-769. https://doi.org/10.1016/j.stemcr.2018.08.002
Abstract
The morphogen FGF8 plays a pivotal role in neocortical area patterning through its inhibitory effect on COUP-TFI/Nr2f1 anterior expression, but its mechanism of action is poorly understood. We established an in vitro model of mouse embryonic stem cell corticogenesis in which COUP-TFI protein expression is inhibited by the activation of FGF8 in a time window corresponding to cortical area patterning. Interestingly, overexpression of the COUP-TFI 3′UTR reduces the inhibitory effect of FGF8 on COUP-TFI translation. FGF8 induces the expression of few miRNAs targeting COUP-TFI 3′UTR in silico. We found that the functional inhibition of miR-21 can effectively counteract the inhibitory effect of FGF8 in vitro and regulate COUP-TFI protein levels in vivo. Accordingly, miR-21 expression is complementary to COUP-TFI expression during corticogenesis. These data support a translational control of COUP-TFI gradient expression by FGF8 via miR-21 and contribute to our understanding of how regionalized expression is established during neocortical area mapping.
Keywords
COUP-TFI, ESC, FGF8, Nr2f1, cortex, corticogenesis, in utero electroporation, mir-21, patterning, Animals, Body Patterning, COUP Transcription Factor I, Cell Differentiation, Cerebral Cortex, Fibroblast Growth Factor 8, Gene Expression Regulation, Developmental, Mice, MicroRNAs, Mouse Embryonic Stem Cells, Protein Biosynthesis
Identifiers
External DOI: https://doi.org/10.1016/j.stemcr.2018.08.002
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285596
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