Premium
Identification of potential target genes for RFX4_v3, a transcription factor critical for brain development
Author(s) -
Zhang Donghui,
Stumpo Deborah J.,
Graves Joan P.,
DeGraff Laura M.,
Grissom Sherry F.,
Collins Jennifer B.,
Li Leping,
Zeldin Darryl C.,
Blackshear Perry J.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03930.x
Subject(s) - biology , gene , wnt signaling pathway , transcription factor , genetics , promoter , tbx1 , microbiology and biotechnology , gene expression
Regulatory factor X4 variant transcript 3 ( Rfx4_v3 ) gene disruption in mice demonstrated that interruption of a single allele (heterozygous, +/–) prevented formation of the subcommissural organ, resulting in congenital hydrocephalus, while interruption of two alleles (homozygous, –/–) caused fatal failure of dorsal midline brain structure formation. To identify potential target genes for RFX4_v3, we used microarray analysis to identify differentially expressed genes in Rfx4_v3 ‐deficient mouse brains at embryonic day 10.5, before gross structural changes were apparent. Of 109 differentially expressed transcripts, 24 were chosen for validation and 22 were confirmed by real‐time PCR. Many validated genes encoded critical proteins involved in brain morphogenesis, such as the signaling components in the Wnt, bone morphogenetic protein (BMP) and retinoic acid (RA) pathways. Cx3cl1 , a CX3C‐type chemokine gene that is highly expressed in brain, was down‐regulated in the Rfx4_v3 ‐null mice. Both human and mouse Cx3cl1 proximal promoters contained highly conserved X‐boxes, known cis ‐acting elements for RFX protein binding. Using the Cx3cl1 promoter as an example of a target gene, we demonstrated direct binding of RFX4_v3 to the Cx3cl1 promoter, and trans ‐acting activity of RFX4_v3 protein to stimulate gene expression. These data suggest that RFX4_v3 may act upstream of critical signaling pathways in the process of brain development.