MiR-30e and miR-181d control Radial Glia cell proliferation via HtrA1 modulation

A. Nigro, R. Menon, A. Bergamaschi, Y. M. Clovis, A. Baldi, M. Ehrmann, G. Comi, D. De Pietri Tonelli, C. Farina, G. Martino, L. Muzio

Research output: Contribution to journalArticlepeer-review

Abstract

The precise mechanisms by which microRNAs (miRNAs) contribute to the dynamic regulation of gene expression during the forebrain development are still partly elusive. Here we show that the depletion of miRNAs in the cerebral cortex and hippocampus, via genetic inactivation of Dicer after the onset of forebrain neurogenesis, profoundly impairs the morphological and proliferative characteristics of neural stem and progenitor cells. The cytoarchitecture and self-renewal potential of radial glial (RG) cells located within the cerebral cortex and the hippocampus were profoundly altered, thus causing a significant derangement of both the post natal dorsal sub-ventricular zone and the dentate gyrus. This effect was attributed to the High-temperature requirement A serine peptidase 1 (HtrA1) gene product whose overexpression in the developing forebrain recapitulated some of the aspects of the Dicer -/- phenotype. MiR-30e and miR-181d were identified as posttranscriptional negative regulators of HtrA1 by binding to its 3′ untranslated region. In vivo overexpression of miR-30e and miR-181d in Dicer -/- forebrain rescued RG proliferation defects.

Original languageEnglish
Article numbere360
JournalCell Death and Disease
Volume3
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Dicer
  • HtrA1
  • MiR-181d
  • MiR-30e
  • Neurogenesis

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Fingerprint Dive into the research topics of 'MiR-30e and miR-181d control Radial Glia cell proliferation via HtrA1 modulation'. Together they form a unique fingerprint.

Cite this