The microRNA miR-21 Is a Mediator of FGF8 Action on Cortical COUP-TFI Translation.
Stem Cell Reports. 2018 Sep 11;11(3):756-769. doi: 10.1016/j.stemcr.2018.08.002. Epub 2018 Aug 30.
Terrigno M1, Bertacchi M2, Pandolfini L1, Baumgart M3, Calvello M1, Cellerino A4, Studer M2, Cremisi F5.
1. Scuola Normale Superiore, Piazza dei Cavalieri, 7, Pisa 56126, Italy.
2. Université Côte d’Azur (UCA), CNRS, Inserm, iBV, 06108 Nice, France.
3. Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
4. Scuola Normale Superiore, Piazza dei Cavalieri, 7, Pisa 56126, Italy; Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745 Jena, Germany.
5. Scuola Normale Superiore, Piazza dei Cavalieri, 7, Pisa 56126, Italy; Istituto di Biofisica CNR, Via Moruzzi 1, 56124 Pisa, Italy. Electronic address: email@example.com.
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.