This article is a US Government work and, as such, is in the public domain in the United States of America.
Regulatory factor X4 variant 3: A transcription factor involved in brain development and disease†
Article first published online: 17 MAY 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 85, Issue 16, pages 3515–3522, December 2007
How to Cite
Zhang, D., Zeldin, D. C. and Blackshear, P. J. (2007), Regulatory factor X4 variant 3: A transcription factor involved in brain development and disease. J. Neurosci. Res., 85: 3515–3522. doi: 10.1002/jnr.21356
- Issue published online: 20 NOV 2007
- Article first published online: 17 MAY 2007
- Manuscript Accepted: 9 MAR 2007
- Manuscript Revised: 22 FEB 2007
- Manuscript Received: 14 NOV 2006
- Intramural Research Program of the NIH, National Institute of Environmental Health Sciences
- regulatory factor X;
- brain development
Regulatory factor X4 variant 3 (RFX4_v3) is a recently identified transcription factor specifically expressed in the brain. Gene disruption in mice demonstrated that interruption of a single allele (heterozygous, +/–) prevented formation of the subcommissural organ (SCO), resulting in congenital hydrocephalus, whereas interruption of two alleles (homozygous, –/–) caused fatal failure of dorsal midline brain structure formation. These mutagenesis studies implicated RFX4_v3 in early brain development as well as the genesis of the SCO. Rfx4_v3 deficiency presumably causes abnormalities in brain by altering the expression levels of many genes that are crucial for brain morphogenesis, such as the signaling components in the Wnt, bone morphogenetic protein, and retinoic acid pathways. RFX4_v3 might affect these critical signaling pathways in brain development. Cx3cl1, a chemokine gene highly expressed in brain, was identified as a direct target for RFX4_v3, indicating that RFX4_v3 possesses trans-acting activity to stimulate gene expression. Rfx4_v3 is highly expressed in the suprachiasmatic nucleus and might be involved in regulating the circadian clock. One haplotype in RFX4_v3 gene is linked to a higher risk of bipolar disorder, suggesting that this protein might contribute to the pathogenesis of the disease. This Mini-Review describes our current knowledge about RFX4_v3, an important protein that appears to be involved in many aspects of brain development and disease. © 2007 Wiley-Liss, Inc.