miR-1224 Controls Mammal Cerebral Cortex Development by Targeting the 3'-UTR of the Dlx1 mRNA

J Cell Physiol. 2025 Jan;240(1):e31511. doi: 10.1002/jcp.31511.

Abstract

Neural precursor cells (NPCs) are a group of cells with self-renewal and multi-differentiation potential. MicroRNAs are required for neurogenesis in the central nervous system (CNS). Recent reports suggest that miR-1224 is important in human CNS diseases. However, its function in neurogenesis of brain development is unclear. The current study demonstrated the essential while developing the neocortex. The results showed that miR-1224 facilitated more NPCs to differentiate into neurons and oligodendrocytes while suppressing astrocyte differentiation. Conversely, inhibition of miR-1224 enhances the self-renewal ability and apoptosis of NPCs. The role of miR-1224 in the developing neocortex was examined by performing in-utero electroporation in vivo. It was observed that depletion impeded upper-layer Cux1+ neuronal generation while transforming radial glial cells into IPCs. However, miR-1224 promoted NPC proliferation in the ventricular zone. Moreover, miR-1224 negatively regulated the expression of Dlx1 in NPCs by directly targeting the mRNA 3'-UTR region. These findings indicated that miR-1224 is a crucial NPC neurogenesis regulator during cortical development.

Keywords: Cux1+ neurons; Dlx1; NPCs; in utero electroporation; miR‐1224; neurogenesis; transformation.

MeSH terms

  • 3' Untranslated Regions* / genetics
  • Animals
  • Apoptosis / genetics
  • Cell Differentiation* / genetics
  • Cell Proliferation* / genetics
  • Cerebral Cortex* / metabolism
  • Ependymoglial Cells / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Homeodomain Proteins* / genetics
  • Homeodomain Proteins* / metabolism
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neural Stem Cells* / metabolism
  • Neurogenesis* / genetics
  • Neurons / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • MicroRNAs
  • Homeodomain Proteins
  • Distal-less homeobox proteins
  • Transcription Factors
  • 3' Untranslated Regions
  • RNA, Messenger