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: Frederique Zindy, Youngsoo Lee, Daisuke Kawauchi, Olivier Ayrault, Leila Ben Merzoug, Yang Li, Peter J McKinnon, Martine F Roussel
• Journal: PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0129642 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26091048 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• Nestin
• Tumor Suppressor Protein p53
• Ribonuclease III

Topics

• Animals
• Apoptosis (genetics)
• Cell Line
• Cell Transformation, Neoplastic (genetics, metabolism)
• Cerebellum (embryology, metabolism, pathology)
• Cerebral Cortex (metabolism, pathology)
• Gene Deletion
• Gene Knockout Techniques
• Medulloblastoma (genetics, metabolism, pathology)
• Mice
• Mice, Transgenic
• MicroRNAs (genetics)
• Nestin (genetics, metabolism)
• Neural Stem Cells (metabolism)
• Phenotype
• Ribonuclease III (genetics, metabolism)
• Stem Cells (metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)