Dataset Information


MiR-29b controls fetal mouse neurogenesis by regulating ICAT-mediated Wnt/β-catenin signaling.

ABSTRACT: β-Catenin has been widely implicated in the regulation of mammalian development and cellular homeostasis. However, the mechanisms by which Wnt/β-catenin signaling components regulate physiological events during brain development remain undetermined. Inactivation of glycogen synthase kinase (GSK)-3β leads to β-catenin accumulation in the nucleus, where it couples with T-cell factor (TCF), an association that is disrupted by ICAT (inhibitor of β-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 β-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/β-catenin signaling.


PROVIDER: S-EPMC4237260 | BioStudies | 2014-01-01

SECONDARY ACCESSION(S): 10.1038/cddis.2014.439

REPOSITORIES: biostudies

Similar Datasets

2000-01-01 | S-EPMC316784 | BioStudies
2020-01-01 | S-EPMC7225968 | BioStudies
2016-01-01 | S-EPMC4823602 | BioStudies
2008-01-01 | S-EPMC2636704 | BioStudies
2018-01-01 | S-EPMC5974619 | BioStudies
1000-01-01 | S-EPMC5029685 | BioStudies
2008-01-01 | S-EPMC2667964 | BioStudies
1000-01-01 | S-EPMC4745698 | BioStudies
2017-01-01 | S-EPMC5342195 | BioStudies
2016-01-01 | S-EPMC4922628 | BioStudies