title: Cerebellar neurodegeneration in the absence of microRNAs.
abstract: Genome-encoded microRNAs (miRNAs) are potent regulators of gene expression. The significance of miRNAs in various biological processes has been suggested by studies showing an important role of these small RNAs in regulation of cell differentiation. However, the role of miRNAs in regulation of differentiated cell physiology is not well established. Mature neurons express a large number of distinct miRNAs, but the role of miRNAs in postmitotic neurons has not been examined. Here, we provide evidence for an essential role of miRNAs in survival of differentiated neurons. We show that conditional Purkinje cell-specific ablation of the key miRNA-generating enzyme Dicer leads to Purkinje cell death. Deficiency in Dicer is associated with progressive loss of miRNAs, followed by cerebellar degeneration and development of ataxia. The progressive neurodegeneration in the absence of Dicer raises the possibility of an involvement of miRNAs in neurodegenerative disorders.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience and 2Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Schaefer
authors.forename: Dónal
authors.initials: D
authors.lastname: O'Carroll
authors.forename: Chan Lek
authors.initials: CL
authors.lastname: Tan
authors.forename: Dean
authors.initials: D
authors.lastname: Hillman
authors.forename: Mutsuyuki
authors.initials: M
authors.lastname: Sugimori
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Llinas
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002531:Cerebellum / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009410:Nerve Degeneration / Q000473:pathology*; D011689:Purkinje Cells / Q000473:pathology
chemical_list: D035683:MicroRNAs