Merck
  • Home
  • Search Results
  • Stage-specific modulation of cortical neuronal development by Mmu-miR-134.

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

Cerebral cortex (New York, N.Y. : 1991) (2011-01-14)
Philip Gaughwin, Maciej Ciesla, Henry Yang, Bing Lim, Patrik Brundin
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-MAP2 (2a+2b) antibody, Mouse monoclonal, clone AP-20, ascites fluid
Sigma-Aldrich
Anti-Glial Fibrillary Acidic Protein antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Anti-Histone H2A.X Antibody, serum, Upstate®
Sigma-Aldrich
Anti-phospho-Histone H2A.X (Ser139) Antibody, clone JBW301, clone JBW301, Upstate®, from mouse