MiR-29b controls fetal mouse neurogenesis by regulating ICAT-mediated Wnt/beta-catenin signaling
- Authors
- Shin, J.; Shin, Y.; Oh, S-M; Yang, H.; Yu, W-J; Lee, J-P; Huh, S-O; Lee, S. H.; Suh, Y-H; Chung, S.; Kim, H-S
- Issue Date
- 10월-2014
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- CELL DEATH & DISEASE, v.5
- Indexed
- SCIE
SCOPUS
- Journal Title
- CELL DEATH & DISEASE
- Volume
- 5
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/97156
- DOI
- 10.1038/cddis.2014.439
- ISSN
- 2041-4889
- Abstract
- 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)-3 beta 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.
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