Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.

<h4>Background</h4>The small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation, identity and survival. To date, however, little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, particularly in the ad...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Véronique Dorval, Pascal Y Smith, Charlotte Delay, Ezequiel Calvo, Emmanuel Planel, Nadège Zommer, Luc Buée, Sébastien S Hébert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b602120e0d1b4ae6927a5bb7395e5045
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b602120e0d1b4ae6927a5bb7395e5045
record_format	dspace
spelling	oai:doaj.org-article:b602120e0d1b4ae6927a5bb7395e50452021-11-18T07:07:28ZGene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.1932-620310.1371/journal.pone.0044060https://doaj.org/article/b602120e0d1b4ae6927a5bb7395e50452012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22952873/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation, identity and survival. To date, however, little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, particularly in the adult mammalian brain.<h4>Methodology/principal findings</h4>We analyzed whole genome microarrays from mice lacking Dicer, the enzyme responsible for miRNA production, specifically in postnatal forebrain neurons. A total of 755 mRNA transcripts were significantly (P<0.05, FDR<0.25) misregulated in the conditional Dicer knockout mice. Ten genes, including Tnrc6c, Dnmt3a, and Limk1, were validated by real time quantitative RT-PCR. Upregulated transcripts were enriched in nonneuronal genes, which is consistent with previous studies in vitro. Microarray data mining showed that upregulated genes were enriched in biological processes related to gene expression regulation, while downregulated genes were associated with neuronal functions. Molecular pathways associated with neurological disorders, cellular organization and cellular maintenance were altered in the Dicer mutant mice. Numerous miRNA target sites were enriched in the 3'untranslated region (3'UTR) of upregulated genes, the most significant corresponding to the miR-124 seed sequence. Interestingly, our results suggest that, in addition to miR-124, a large fraction of the neuronal miRNome participates, by order of abundance, in coordinated gene expression regulation and neuronal maintenance.<h4>Conclusions/significance</h4>Taken together, these results provide new clues into the role of specific miRNA pathways in the regulation of brain identity and maintenance in adult mice.Véronique DorvalPascal Y SmithCharlotte DelayEzequiel CalvoEmmanuel PlanelNadège ZommerLuc BuéeSébastien S HébertPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e44060 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Véronique Dorval Pascal Y Smith Charlotte Delay Ezequiel Calvo Emmanuel Planel Nadège Zommer Luc Buée Sébastien S Hébert Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.
description	<h4>Background</h4>The small non-protein-coding microRNAs (miRNAs) have emerged as critical regulators of neuronal differentiation, identity and survival. To date, however, little is known about the genes and molecular networks regulated by neuronal miRNAs in vivo, particularly in the adult mammalian brain.<h4>Methodology/principal findings</h4>We analyzed whole genome microarrays from mice lacking Dicer, the enzyme responsible for miRNA production, specifically in postnatal forebrain neurons. A total of 755 mRNA transcripts were significantly (P<0.05, FDR<0.25) misregulated in the conditional Dicer knockout mice. Ten genes, including Tnrc6c, Dnmt3a, and Limk1, were validated by real time quantitative RT-PCR. Upregulated transcripts were enriched in nonneuronal genes, which is consistent with previous studies in vitro. Microarray data mining showed that upregulated genes were enriched in biological processes related to gene expression regulation, while downregulated genes were associated with neuronal functions. Molecular pathways associated with neurological disorders, cellular organization and cellular maintenance were altered in the Dicer mutant mice. Numerous miRNA target sites were enriched in the 3'untranslated region (3'UTR) of upregulated genes, the most significant corresponding to the miR-124 seed sequence. Interestingly, our results suggest that, in addition to miR-124, a large fraction of the neuronal miRNome participates, by order of abundance, in coordinated gene expression regulation and neuronal maintenance.<h4>Conclusions/significance</h4>Taken together, these results provide new clues into the role of specific miRNA pathways in the regulation of brain identity and maintenance in adult mice.
format	article
author	Véronique Dorval Pascal Y Smith Charlotte Delay Ezequiel Calvo Emmanuel Planel Nadège Zommer Luc Buée Sébastien S Hébert
author_facet	Véronique Dorval Pascal Y Smith Charlotte Delay Ezequiel Calvo Emmanuel Planel Nadège Zommer Luc Buée Sébastien S Hébert
author_sort	Véronique Dorval
title	Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.
title_short	Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.
title_full	Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.
title_fullStr	Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.
title_full_unstemmed	Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.
title_sort	gene network and pathway analysis of mice with conditional ablation of dicer in post-mitotic neurons.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b602120e0d1b4ae6927a5bb7395e5045
work_keys_str_mv	AT veroniquedorval genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons AT pascalysmith genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons AT charlottedelay genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons AT ezequielcalvo genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons AT emmanuelplanel genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons AT nadegezommer genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons AT lucbuee genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons AT sebastienshebert genenetworkandpathwayanalysisofmicewithconditionalablationofdicerinpostmitoticneurons
_version_	1718423936476119040

Gene network and pathway analysis of mice with conditional ablation of Dicer in post-mitotic neurons.

Ejemplares similares