Altered gene expression in the emerging cerebellar primordium of Neurog1-/- mice.
Summary of "Altered gene expression in the emerging cerebellar primordium of Neurog1-/- mice."
Expression of the basic helix-loop-helix (bHLH) transcription factor Neurogenin1 (Neurog1) coincides with the emergence of the cerebellum and Neurog1-expressing progenitors are fated to become Purkinje cells and later interneurons. However, the gene regulatory functions of Neurog1 in cerebellar development have not been characterized. We performed a genome-wide analysis of gene expression in the cerebellar primordium of E11.5 Neurog1 null (Neurog1-/-) mice to identify the Neurog1 transcriptome in the emerging cerebellum. This screen identified 117 genes differentially enriched in Neurog1-/- versus control sample sets with a high presence of gene sets enriched for functions in nervous system development. Hierarchical clustering revealed complete stratification of differentially expressed genes based on Neurog1 gene deletion status. In silico analysis of promoter regions identifies high probability Neurog1 regulatory (E-box) binding sites in 94 of the 117 differentially expressed genes and Pax6 binding motifs in 25 of these 94 promoters. Our data provide a framework for investigating Neurog1 transcriptional programs in early cerebellar development and suggest functional Neurog1-Pax6 cross-talk in the activation of downstream targets.
Affiliation
Journal Details
This article was published in the following journal.
Name: Brain research
ISSN: 1872-6240
Pages: 12-21
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21382351
- DOI: http://dx.doi.org/10.1016/j.brainres.2011.02.087
Medical and Biotech [MESH] Definitions
Mice, Inbred Cftr
A strain of mice widely studied as a model for cystic fibrosis. These mice are generated from embryonic stem cells in which the CFTR (cystic fibrosis transmembrane conductance regulator) gene is inactivated by gene targeting. As a result, all mice have one copy of this altered gene in all their tissues. Mice homozygous for the disrupted gene exhibit many features common to young cystic fibrosis patients, including failure to thrive, meconium ileus, and alteration of mucous and serous glands.
Mice, Knockout
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Epistasis, Genetic
A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.
Gene Knock-in Techniques
Techniques used to add in exogenous gene sequence such as mutated genes; REPORTER GENES, to study mechanisms of gene expression; or regulatory control sequences, to study effects of temporal changes to GENE EXPRESSION.
Gene Dosage
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
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