Organizational Principles of the Connexin-Related Brain Transcriptome

Abstract

We have found that deletion of genes encoding the gap junction proteins Cx43, Cx32 and Cx36 alter the expression levels of large numbers of genes in mouse brain located on all chromosomes and encoding proteins from all major functional categories. Gene regulation in Cx32 and Cx43 null brains was more similar than that in the Cx36 null brain, suggesting the possibility of transcriptomic controls exerted by both genes on both astrocytes and oligodendrocytes. In order to explore the nature of expression linkage among the genes, we examined coordinated expression patterns in wild-type and connexin null brains. Coordination with Cx43 in wild-type brain predicted regulation in Cx43 nulls with considerable accuracy. Moreover, interlinkage within gene networks was greatly perturbed in the Cx43 null brain. These findings suggest several principles regarding regulatory transcriptomic networks involving gap junction genes and raise the issue of the underlying cause of connexin null phenotypes as well as mechanisms of regulation.