Gene expression analysis of nuclear factor I-A deficient mice indicates delayed brain maturation
1 Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany
2 Institut für Klinische Chemie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany
3 Department of Biochemistry and Program in Neuroscience, State University of New York at Buffalo, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA
4 Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, D-251, Piscataway, NJ 08854, USA
Citation and License
Genome Biology 2007, 8:R72 doi:10.1186/gb-2007-8-5-r72Published: 2 May 2007
Nuclear factor I-A (NFI-A), a phylogenetically conserved transcription/replication protein, plays a crucial role in mouse brain development. Previous studies have shown that disruption of the Nfia gene in mice leads to perinatal lethality, corpus callosum agenesis, and hydrocephalus.
To identify potential NFI-A target genes involved in the observed tissue malformations, we analyzed gene expression in brains from Nfia-/- and Nfia+/+ littermate mice at the mRNA level using oligonucleotide microarrays. In young postnatal animals (postnatal day 16), 356 genes were identified as being differentially regulated, whereas at the late embryonic stage (embryonic day 18) only five dysregulated genes were found. An in silico analysis identified phylogenetically conserved NFI binding sites in at least 70 of the differentially regulated genes. Moreover, assignment of gene function showed that marker genes for immature neural cells and neural precursors were expressed at elevated levels in young postnatal Nfia-/- mice. In contrast, marker genes for differentiated neural cells were downregulated at this stage. In particular, genes relevant for oligodendrocyte differentiation were affected.
Our findings suggest that brain development, especially oligodendrocyte maturation, is delayed in Nfia-/- mice during the early postnatal period, which at least partly accounts for their phenotype. The identification of potential NFI-A target genes in our study should help to elucidate NFI-A dependent transcriptional pathways and contribute to enhanced understanding of this period of brain formation, especially with regard to the function of NFI-A.