Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation

Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation

Dicer, a ribonuclease III enzyme, is required for the maturation of microRNAs. To assess its role in cerebellar and medulloblastoma development, we genetically deleted Dicer in Nestin-positive neural progenitors and in mice lacking one copy for the Sonic Hedgehog receptor, Patched 1. We found that c...

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Main Authors: Zindy, Frederique, Lee, Youngsoo, Kawauchi, Daisuke, Ayrault, Olivier, Merzoug, Leila Ben, Li, Yang, McKinnon, Peter J., Roussel, Martine F.
Format: Online
Language:English
Published: Public Library of Science 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474721/
id pubmed-4474721
recordtype oai_dc
spelling pubmed-44747212015-06-30 Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation Zindy, Frederique Lee, Youngsoo Kawauchi, Daisuke Ayrault, Olivier Merzoug, Leila Ben Li, Yang McKinnon, Peter J. Roussel, Martine F. Research Article Dicer, a ribonuclease III enzyme, is required for the maturation of microRNAs. To assess its role in cerebellar and medulloblastoma development, we genetically deleted Dicer in Nestin-positive neural progenitors and in mice lacking one copy for the Sonic Hedgehog receptor, Patched 1. We found that conditional loss of Dicer in mouse neural progenitors induced massive Trp53-independent apoptosis in all proliferative zones of the brain and decreased proliferation of cerebellar granule progenitors at embryonic day 15.5 leading to abnormal cerebellar development and perinatal lethality. Loss of one copy of Dicer significantly accelerated the formation of mouse medulloblastoma of the Sonic Hedgehog subgroup in Patched1-heterozygous mice. We conclude that Dicer is required for proper cerebellar development, and to restrain medulloblastoma formation. Public Library of Science 2015-06-19 /pmc/articles/PMC4474721/ /pubmed/26091048 http://dx.doi.org/10.1371/journal.pone.0129642 Text en © 2015 Zindy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zindy, Frederique
Lee, Youngsoo
Kawauchi, Daisuke
Ayrault, Olivier
Merzoug, Leila Ben
Li, Yang
McKinnon, Peter J.
Roussel, Martine F.
spellingShingle Zindy, Frederique
Lee, Youngsoo
Kawauchi, Daisuke
Ayrault, Olivier
Merzoug, Leila Ben
Li, Yang
McKinnon, Peter J.
Roussel, Martine F.
Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation
author_facet Zindy, Frederique
Lee, Youngsoo
Kawauchi, Daisuke
Ayrault, Olivier
Merzoug, Leila Ben
Li, Yang
McKinnon, Peter J.
Roussel, Martine F.
author_sort Zindy, Frederique
title Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation
title_short Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation
title_full Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation
title_fullStr Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation
title_full_unstemmed Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation
title_sort dicer is required for normal cerebellar development and to restrain medulloblastoma formation
description Dicer, a ribonuclease III enzyme, is required for the maturation of microRNAs. To assess its role in cerebellar and medulloblastoma development, we genetically deleted Dicer in Nestin-positive neural progenitors and in mice lacking one copy for the Sonic Hedgehog receptor, Patched 1. We found that conditional loss of Dicer in mouse neural progenitors induced massive Trp53-independent apoptosis in all proliferative zones of the brain and decreased proliferation of cerebellar granule progenitors at embryonic day 15.5 leading to abnormal cerebellar development and perinatal lethality. Loss of one copy of Dicer significantly accelerated the formation of mouse medulloblastoma of the Sonic Hedgehog subgroup in Patched1-heterozygous mice. We conclude that Dicer is required for proper cerebellar development, and to restrain medulloblastoma formation.
publisher Public Library of Science
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474721/
_version_ 1613238073059966976

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