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Stage-Specific Modulation of Cortical Neuronal Development by Mmu-miR-134

In English

Författare

  • Philip Gaughwin
  • Maciej Ciesla
  • Henry Yang
  • Bing Lim
  • Patrik Brundin

Summary, in English

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.

Publiceringsår

2011

Språk

Engelska

Sidor

1857-1869

Publikation/Tidskrift/Serie

Cerebral Cortex

Volym

21

Issue

8

Dokumenttyp

Artikel i tidskrift

Förlag

Oxford University Press

Ämne

  • Neurosciences

Nyckelord

  • cortex
  • migration
  • microRNAs
  • mmu-miR-134

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1460-2199