| 2004 |
RFX3 is required for the development of nodal monocilia and left-right body axis determination; Rfx3-deficient mice show stunted nodal cilia and left-right asymmetry defects. RFX3 regulates expression of D2lic (mouse orthologue of a C. elegans intraflagellar transport gene), establishing RFX3 as an upstream transcriptional regulator of intraflagellar transport-dependent ciliogenesis. |
Rfx3 knockout mouse, RT-PCR for D2lic expression, electron microscopy of nodal cilia |
Molecular and cellular biology |
High |
15121860
|
| 2006 |
RFX3 is necessary for differentiation of ciliated ependymal cells in the mouse brain; Rfx3-deficient mice develop hydrocephalus associated with defects in choroid plexus epithelial organization and agenesis of the subcommissural organ (SCO), with downregulation of SCO-spondin expression as early as E14.5. |
Rfx3 knockout mouse, ultrastructural analysis (electron microscopy), immunohistochemistry, RT-PCR |
The European journal of neuroscience |
High |
16930429
|
| 2007 |
RFX3 is expressed in pancreatic endocrine progenitors and all major islet lineages; Rfx3-deficient mice show reduced insulin-, glucagon-, and ghrelin-producing cells with increased pancreatic polypeptide-positive cells, and primary cilia on islet cells are severely stunted, indicating RFX3 controls endocrine cell differentiation and cilia formation in the pancreas. |
Rfx3 knockout mouse, immunofluorescence, glucose tolerance tests, electron microscopy of primary cilia |
Diabetes |
High |
17229940
|
| 2009 |
RFX3 is required for growth and beating efficiency of motile cilia in multiciliated brain cells. RFX3 promotes optimal expression of the FOXJ1 transcription factor and directly binds promoters of axonemal dynein genes to regulate their expression, linking RFX3 to ciliary motility programs. |
Primary multiciliated cell culture from Rfx3-/- mouse brain, cilia motility assays, ChIP (direct promoter binding of dynein genes), RT-PCR for FOXJ1 |
Journal of cell science |
High |
19671664
|
| 2010 |
RFX3 is required for differentiation and function of mature beta-cells; it directly binds the Pal-1 and Pal-2 regulatory sequences in the neuroendocrine promoter of the glucokinase (Gck) gene, regulating Glut-2 and Gck expression. Loss of Rfx3 leads to accumulation of incompletely differentiated beta-cell precursors and glucose intolerance. |
Rfx3 knockout and pancreas-specific conditional knockout mice, quantitative ChIP, ChIP sequencing, bandshift assay, RNA interference in Min6 cells, immunofluorescence, RT-PCR |
Diabetes |
High |
20413507
|
| 2012 |
RFX3 indirectly regulates corpus callosum formation by controlling patterning of the cortical-septal boundary required for distribution of midline guidepost neurons. Rfx3 deficiency leads to ectopic FGF8 expression at the rostro-commissural plate associated with a reduced GLI3 repressor-to-activator ratio, and ectopic FGF8 reproduces guidepost neuronal defects. |
Rfx3 knockout mouse, conditional genetic inactivation, brain explant cultures with ectopic FGF8, transplantation assays, immunohistochemistry, in situ hybridization |
PLoS genetics |
High |
22479201
|
| 2013 |
RFX3 physically interacts with FOXJ1 (demonstrated by co-immunoprecipitation) and acts as a transcriptional co-activator; combined FOXJ1 + RFX3 transfection enhances cilia gene promoter activity and mRNA expression beyond FOXJ1 alone. RFX3 alone does not induce FOXJ1 expression or cilia gene expression. |
Plasmid-mediated gene transfer into human airway basal cells, co-immunoprecipitation, promoter-reporter assays, TaqMan RT-PCR |
Respiratory research |
Medium |
23822649
|
| 2015 |
Rfx3 is required for proper patterning of the prethalamus and ventral telencephalon necessary for thalamocortical tract formation; Rfx3-deficient mice show misguided thalamocortical axons associated with heterotopias expressing Slit1 and Netrin1 guidance molecules. Identical defects in Inpp5e mutants corroborate a role for primary cilia signaling in this process. |
Rfx3 knockout mouse, DiI axon tracing, immunohistochemistry, comparison with Inpp5e mutant mice |
Human molecular genetics |
Medium |
25631876
|
| 2018 |
RFX3 transcriptional activity is regulated by S-fatty acylation at a conserved cysteine residue in its dimerization domain. RFX3 undergoes enzyme-independent auto-fatty acylation with preference for 18-carbon stearic and oleic acids. A fatty acylation-deficient mutant shows decreased homodimerization, fails to promote ciliary gene expression and ciliogenesis, and impairs Hedgehog signaling. |
Chemical reporters of protein fatty acylation, mass spectrometry, site-directed mutagenesis of the conserved cysteine, ciliogenesis assays, Hedgehog signaling reporter assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
30127002
|
| 2018 |
RFX1 homodimers and RFX1/RFX3 heterodimers bind specifically to the double-stranded D sequence of AAV2 and AAV1 inverted terminal repeats; RFX3 antibodies can pull down AAV genomes from transduced HEK-293 cells, indicating RFX3 interacts with AAV genomes in the nucleus and acts as a regulator of AAV-mediated transgene expression. |
Electromobility shift assay (EMSA), supershift experiments with RFX1/RFX3 antibodies, chromatin immunoprecipitation of AAV genomes from HEK-293 cells |
Scientific reports |
Medium |
29317724
|
| 2025 |
In human iPSC-derived neurons, RFX3 binding sites co-localize with CREB binding sites near activity-dependent genes. Monoallelic RFX3 loss reduces CREB binding at activity-dependent enhancers and impairs induction of CREB targets upon neuronal depolarization, placing RFX3 as a co-regulator that facilitates activity-dependent transcription by enhancing CREB chromatin binding. |
iPSC-derived neurons and forebrain organoids with CRISPR RFX3 loss-of-function, transcriptomics, ChIP-seq for RFX3 and CREB binding, neuronal depolarization assays |
bioRxivpreprint |
Medium |
40060598
|
| 2025 |
RFX3 interacts with MEF2C and CREB1/CRTC1 in an activity-dependent manner in neurons. Upon glutamatergic stimulation, CRTC1 and CREB1 are recruited to activity-dependent enhancers enriched for RFX3 motifs, suggesting cooperative chromatin binding between CREB1 and RFX3 in response to synaptic activity. |
Proximity labeling (BioID) in rodent forebrain neurons, ChIP-seq for CREB1 and CRTC1 before and after glutamatergic stimulation, motif enrichment analysis |
bioRxivpreprint |
Medium |
40631264
|
| 2025 |
RFX3 is required for human pancreatic islet cell differentiation from iPSCs; RFX3 KO disrupts endocrine gene regulation, reduces hormone-secreting islet cells, impairs beta-cell function and insulin secretion, increases enterochromaffin cell specification, and increases apoptosis. RFX3 overexpression rescues dysregulated gene expression at progenitor stages. |
CRISPR/Cas9 RFX3 KO iPSC lines differentiated into pancreatic islet organoids, scRNA-seq, bulk RNA-seq, glucose-stimulated insulin secretion assays, RFX3 overexpression rescue |
Diabetologia |
High |
40263183
|
| 2024 |
Rfx3 functions as both a transcriptional activator and repressor in cochlear outer hair cells, binding to the intronic enhancer of the hair bundle gene Triobp to regulate its spatiotemporal expression, and binding to differentiation/fate determination genes Tbx2, Insm1, and Ikzf2. Rfx3 and Rfx7 show dynamic subcellular localization shifting from nuclear to cytoplasmic at later developmental stages. |
Single-cell transcriptomics, ChIP-seq, ATAC-seq in cochlear hair cells; conditional Rfx3 knockout mouse (inner ear) |
bioRxivpreprint |
Medium |
|
| 2024 |
RFX3 physically interacts with FOXJ1, FOXN3, and FOXN4 via a short hydrophobic motif (LXXLXWL) shared by these forkhead proteins; this motif binds the RFX3 dimerization domain. Mutations in RFX3 at the predicted interaction site disrupt association. FOXN3 functions as a repressor of cilia genes and limits primary cilia formation through its interaction with RFX3. |
CUT&RUN (chromatin binding), co-IP/pulldown assays, site-directed mutagenesis of RFX3 dimerization domain, AlphaFold3 structural prediction, transcriptional reporter assays in Foxn3 knockout retina |
bioRxivpreprint |
Medium |
|