Identification of potential target genes for RFX4_v3, a transcription factor critical for brain development
Abstract
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.
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Genetic ablation of Rfx4 decreases Gpr56 expression in developing mouse brain.
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- Authors
- Zhang, D., Stumpo, D. J., Graves, J. P., DeGraff, L. M., Grissom, S. F., Collins, J. B., Li, L., Zeldin, D. C., & Blackshear, P. J.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2006-06-26
- Volume
- 98
- Issue
- 3
- Pages
- 860-875
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2125484558
- Cited by
- 37
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 2 · 2019: 1 · 2018: 3 · 2017: 2 · 2015: 2 · 2014: 4 · 2012: 1
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- RFX transcription factors, brain development, subcommissural organ, congenital hydrocephalus, fractalkine, CX3C chemokines, transcription factor target genes, Wnt signaling, BMP signaling, retinoic acid signaling, brain morphogenesis, gene expression profiling
- MeSH terms
- Regulatory Factor X Transcription Factors, Animals, Base Sequence, Brain, Chlorocebus aethiops, DNA-Binding Proteins, Humans, Mice, Inbred C57BL, Molecular Sequence Data, Transcription Factors, Mice, Knockout, Gene Targeting, Gene Expression Regulation, Developmental, COS Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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