title: Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation.
abstract: 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.
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Frederique
authors.initials: F
authors.lastname: Zindy
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawauchi
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ayrault
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Leila Ben
authors.initials: LB
authors.lastname: Merzoug
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McKinnon
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN, United States of America.
authors.forename: Martine F
authors.initials: MF
authors.lastname: Roussel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D002531:Cerebellum / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D010641:Phenotype; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D064231:Nestin; D016159:Tumor Suppressor Protein p53; D043244:Ribonuclease III