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Regional expression of MTG genes in the developing mouse central nervous system.

ABSTRACT: Myeloid translocation gene (MTG) proteins are transcriptional repressors that are highly conserved across species. We studied the expression of three members of this gene family, MTGR1, MTG8, and MTG16 in developing mouse central nervous system by in situ hybridization. All of these genes are detected as early as embryonic day 11.5. Because these genes are known to be induced by proneural genes during neurogenesis, we analyzed the expression of MTG genes in relation to two proneural genes, Neurog2 (also known as Ngn2 or Neurogenin 2) and Ascl1 (also known as Mash1). While MTGR1 are generally expressed in regions that also express Neurog2, MTG8 and MTG16 expression is associated more tightly with that of Ascl1-expressing neural progenitor cells. These results suggest the possibility that expression of MTG genes is differentially controlled by specific proneural genes during neurogenesis.

SUBMITTER: Alishahi A

PROVIDER: S-EPMC2742708 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Regional expression of MTG genes in the developing mouse central nervous system.

Alishahi Amin A Koyano-Nakagawa Naoko N Nakagawa Yasushi Y

Developmental dynamics : an official publication of the American Association of Anatomists 20090801 8

Myeloid translocation gene (MTG) proteins are transcriptional repressors that are highly conserved across species. We studied the expression of three members of this gene family, MTGR1, MTG8, and MTG16 in developing mouse central nervous system by in situ hybridization. All of these genes are detected as early as embryonic day 11.5. Because these genes are known to be induced by proneural genes during neurogenesis, we analyzed the expression of MTG genes in relation to two proneural genes, Neuro ...[more]

PMID: 19618476

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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

Regional expression of MTG genes in the developing mouse central nervous system.

Publications

Regional expression of MTG genes in the developing mouse central nervous system.

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