Gene expression analysis of nuclear factor I-A deficient mice indicates delayed brain maturation.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Wong
Yong Wee
YW
Zentrum für Molekulare Neurobiologie Hamburg, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. yongwee2001@yahoo.com
Schulze
Christian
C
Streichert
Thomas
T
Gronostajski
Richard M
RM
Schachner
Melitta
M
Tilling
Thomas
T
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000254:growth & development*; D002454:Cell Differentiation / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D051839:NFI Transcription Factors / Q000172:deficiency* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology; D014158:Transcription, Genetic
D051839:NFI Transcription Factors; C497646:Nfia protein, mouse