| First Author | Shin J | Year | 2014 |
| Journal | Cell Death Dis | Volume | 5 |
| Issue | 10 | Pages | e1473 |
| PubMed ID | 25321480 | Mgi Jnum | J:345368 |
| Mgi Id | MGI:6838999 | Doi | 10.1038/cddis.2014.439 |
| Citation | Shin J, et al. (2014) MiR-29b controls fetal mouse neurogenesis by regulating ICAT-mediated Wnt/beta-catenin signaling. Cell Death Dis 5:e1473 |
| abstractText | beta-Catenin has been widely implicated in the regulation of mammalian development and cellular homeostasis. However, the mechanisms by which Wnt/beta-catenin signaling components regulate physiological events during brain development remain undetermined. Inactivation of glycogen synthase kinase (GSK)-3beta leads to beta-catenin accumulation in the nucleus, where it couples with T-cell factor (TCF), an association that is disrupted by ICAT (inhibitor of beta-catenin and T cell factor). In this study, we sought to determine whether regulation of ICAT by members of the microRNA-29 family plays a role during neurogenesis and whether deregulation of ICAT results in defective neurogenesis due to impaired beta-catenin-mediated signaling. We found that miR-29b, but not miR-29a or 29c, is significantly upregulated in three-dimensionally cultured neural stem cells (NSCs), whereas ICAT is reduced as aged. Treatment with a miR-29b reduced the reporter activity of a luciferase-ICAT 3'-UTR construct whereas a control (scrambled) miRNA oligonucleotide did not, indicating that miR-29b directly targets the 3'-UTR of ICAT. We also found that treatment with miR-29b diminished NSC self-renewal and proliferation, and controlled their fate, directing their differentiation along certain cell lineages. Furthermore, our in vivo results showed that inhibition of miR-29b by in utero electroporation induced a profound defect in corticogenesis during mouse development. Taken together, our results demonstrate that miR-29b plays a pivotal role in fetal mouse neurogenesis by regulating ICAT-mediated Wnt/beta-catenin signaling. |
