title: Dicer1 and MiR-9 are required for proper Notch1 signaling and the Bergmann glial phenotype in the developing mouse cerebellum.
abstract: MicroRNAs (miRNAs) have important roles in the development of the central nervous system (CNS). Several reports indicate that tissue development and cellular differentiation in the developing forebrain are disrupted in the absence of miRNAs. However, the functions of miRNAs during cerebellar development have not been systematically characterized. Here, we conditionally knocked out the Dicer1 gene under the control of the human glial fibrillary acidic protein (hGFAP) promoter to examine the effect of miRNAs in the developing cerebellum. We particularly focused on the phenotype of Bergmann glia (BG). The hGFAP-Cre activity was detected as early as embryonic day 13.5 (E13.5) at the rhombic lip (RL) in the cerebellar plate, and later in several postnatal cerebellar cell types, including BG. Dicer1 ablation induces a smaller and less developed cerebellum, accompanied by aberrant BG morphology. Notch1 signaling appears to be blocked in Dicer1-ablated BG, with reduced expression of the Notch1 target gene, brain lipid binding protein (BLBP). Using neuronal co-culture assays, we showed an intrinsic effect of Dicer1 on BG morphology and Notch1 target gene expression. We further identified miR-9 as being differentially expressed in BG and showed that miR-9 is a critical, but not the only, miRNA component of the Notch1 signaling pathway in cultured BG cells.
authors: West China Developmental and Stem Cell Institute, West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China.
authors: Yi
authors: Y
authors: Kuang
authors: Qian
authors: Q
authors: Liu
authors: Xiaoqiong
authors: X
authors: Shu
authors: Chi
authors: C
authors: Zhang
authors: Ning
authors: N
authors: Huang
authors: Jun
authors: J
authors: Li
authors: Mei
authors: M
authors: Jiang
authors: Hedong
authors: H
authors: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D018920:Coculture Techniques; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases