Advanced

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

Gaughwin, Philip LU ; Ciesla, Maciej; Yang, Henry; Lim, Bing and Brundin, Patrik LU (2011) In Cerebral Cortex 21(8). p.1857-1869
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cortex, migration, microRNAs, mmu-miR-134
in
Cerebral Cortex
volume
21
issue
8
pages
1857 - 1869
publisher
Oxford University Press
external identifiers
  • wos:000293076300014
  • scopus:79960752625
ISSN
1460-2199
DOI
10.1093/cercor/bhq262
language
English
LU publication?
yes
id
4d8faf67-f6b0-4ac7-bf6b-15c01fc3c4ac (old id 2072381)
date added to LUP
2011-09-02 08:31:37
date last changed
2017-11-05 03:15:59
@article{4d8faf67-f6b0-4ac7-bf6b-15c01fc3c4ac,
  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.},
  author       = {Gaughwin, Philip and Ciesla, Maciej and Yang, Henry and Lim, Bing and Brundin, Patrik},
  issn         = {1460-2199},
  keyword      = {cortex,migration,microRNAs,mmu-miR-134},
  language     = {eng},
  number       = {8},
  pages        = {1857--1869},
  publisher    = {Oxford University Press},
  series       = {Cerebral Cortex},
  title        = {Stage-Specific Modulation of Cortical Neuronal Development by Mmu-miR-134},
  url          = {http://dx.doi.org/10.1093/cercor/bhq262},
  volume       = {21},
  year         = {2011},
}