Stage-specific modulation of cortical neuronal development by Mmu-miR-134

Cereb Cortex. 2011 Aug;21(8):1857-69. doi: 10.1093/cercor/bhq262. Epub 2011 Jan 12.


To realize the potential of microRNAs (miRs) as fine-tuning regulators of embryonic neuronal differentiation, it is critical to define their developmental function. Mmu-miR-134 (miR-134) is a powerful inducer of pluripotent stem cell differentiation. However, its functional role during embryonic, neuronal development is unknown. We demonstrate that mature, miR-134 transcript levels elevate during embryonic, neuronal differentiation in vitro and in vivo. To define the developmental targets and function of miR-134, we identified multiple brain-expressed targets including the neural progenitor cell-enriched, bone morphogenetic protein (BMP) antagonist Chordin-like 1 (Chrdl-1) and the postmitotic, neuron-specific, microtubule-associated protein, Doublecortin (Dcx). We show that, through interaction with Dcx and/or Chrdl-1, miR-134 has stage-specific effects on cortical progenitors, migratory neurons, and differentiated neurons. In neural progenitors, miR-134 promotes cell proliferation and counteracts Chrdl-1-induced apoptosis and Dcx-induced differentiation in vitro. In neurons, miR-134 reduces cell migration in vitro and in vivo in a Dcx-dependent manner. In differentiating neurons, miR-134 modulates process outgrowth in response to exogenous BMP-4 in a noggin-reversible manner. Taken together, we present Dcx and Chrdl-1 as new regulatory targets of miR-134 during embryonic, mouse, cortical, and neuronal differentiation and show a novel and previously undiscovered role for miR-134 in the stage-specific modulation of cortical development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Cycle / physiology*
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology*
  • Cerebral Cortex / physiology
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Targeting / methods
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / physiology*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / physiology
  • Neurogenesis / physiology*
  • Neurons / cytology*
  • Neurons / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism


  • Chrdl1 protein, mouse
  • DCX protein, human
  • Dcx protein, mouse
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Eye Proteins
  • MicroRNAs
  • Microtubule-Associated Proteins
  • Mirn134 microRNA, mouse
  • Nerve Tissue Proteins
  • Neuropeptides