Dataset Information

Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system.

ABSTRACT: MicroRNAs, processed by the RNAase III enzyme Dicer, are approximately 22 nucleotide endogenous noncoding small RNAs. The function of Dicer in the mouse central nervous system (CNS) development is not well understood. Here, we show that specifically deleting Dicer expression in the CNS and in the cerebral cortex using two Cre lines results in reduced progenitor numbers, abnormal neuronal differentiation, and thinner cortical wall. Incomplete Dicer deletion during early embryonic stages contributes to normal development of early-born neurons in the cortex and motor neurons in the spinal cord. However, at late embryonic stages when Dicer is completely ablated in the CNS, the migration of late-born neurons in the cortex and oligodendrocyte precursor expansion and differentiation in the spinal cord are greatly affected. Our studies of different timings of Dicer deletion demonstrate the importance of the Dicer-mediated microRNA pathway in regulating distinct phases of neurogenesis and gliogenesis during the CNS development.

SUBMITTER: Kawase-Koga Y

PROVIDER: S-EPMC2831750 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system.

Kawase-Koga Yoko Y Otaegi Gaizka G Sun Tao T

Developmental dynamics : an official publication of the American Association of Anatomists 20091101 11

MicroRNAs, processed by the RNAase III enzyme Dicer, are approximately 22 nucleotide endogenous noncoding small RNAs. The function of Dicer in the mouse central nervous system (CNS) development is not well understood. Here, we show that specifically deleting Dicer expression in the CNS and in the cerebral cortex using two Cre lines results in reduced progenitor numbers, abnormal neuronal differentiation, and thinner cortical wall. Incomplete Dicer deletion during early embryonic stages contribut ...[more]

PMID: 19806666

Similar Datasets

Project description:Prenatal Human Cytomegalovirus (HCMV) infection often causes CNS maldevelopment. In a murine model, we detect Murine Cytomegalovirus (MCMV) in brain following intra-peritoneal inoculation at birth. Infected mice show impaired cerebellar development and impaired neurologic function on a beam balance test as adults. Among developmental genes differentially regulated, hindbrain expression of the homeodomain transcription factor HOXa5 was reduced with infection, and fewer HOXa5 expressing neurons were found in vestibular nuclei. Based on the hypothesis that immune activation connects focal viral infection and global CNS maldevelopment, we defined the components of CNS immune response. Flow cytometry showed a large increase in both number and activation of CNS monocytes. Monocytes were found in close association with infected cells by immunohistochemistry (IHC). Oligonucleotide microarrays contained herein identified many differentially expressed genes related to innate immune response. Chemokines, cytokines, cell surface receptors, and proteases are some of the many immunological genes shown to be differentially regulated by MCMV infection. These results together show that MCMV infection induces a complex immune response associated with changes in developmental gene expression and lasting neurologic defecit. Keywords: disease state comparison (virus infection) and competetive hybridization for expression analysis Previous work empirically determined the kinetics of viral spread to and replication in the Balb-C murine CNS. Balb-C mice were inoculated intra-peritoneally at birth, and harvested at 5, 8, 12, and 21 days post inoculation for cerebellar experiments. Controls were mock infected with vehicle (DMEM cell growth media) and harvested at the same timepoints. Each microarray was a two channel MEEBO array, upon which labeled and reverse transcribed cDNA from 3 pooled infected cerebella and three pooled uninfected cerebella competetively hybridized. Three unique biological replicates were performed with day 5 cDNA, 5 unique biological replicates at day 8, 5 unique biological replicates at day 12, and 4 unique biological replicates at day 21. For the analysis, colors channels were seperated and treated as independent hybridizations. However, since the experiments were dual channel, the primary data may be employed to generate ratio based measurements, and each sample is provided a corresponding number that can be used to pair the processed data and derive ratios (mock 3, infected 3). Mice were similarly inoculated and harvested at 5, 15, and 21 days post natal for liver tissue analysis. Inoculation was performed by injection with a microsyringe of 50ul titered virus delivering 500-1000 PFU per animal.

Dataset Information

Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system.

Publications

Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure