Stage-Specific Modulation of Cortical Neuronal Development by Mmu-miR-134
(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:
https://lup.lub.lu.se/record/2072381
- author
- Gaughwin, Philip LU ; Ciesla, Maciej ; Yang, Henry ; Lim, Bing and Brundin, Patrik LU
- organization
- publishing date
- 2011
- 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
- pmid:21228099
- ISSN
- 1460-2199
- DOI
- 10.1093/cercor/bhq262
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuronal Survival (013212041)
- id
- 4d8faf67-f6b0-4ac7-bf6b-15c01fc3c4ac (old id 2072381)
- date added to LUP
- 2016-04-01 10:37:38
- date last changed
- 2022-02-10 03:52:25
@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}},
keywords = {{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}},
doi = {{10.1093/cercor/bhq262}},
volume = {{21}},
year = {{2011}},
}