RFX3 and Associated Diseases
Creative Biolabs is a fast-growing business headquartered in New York, USA. In conjunction with pharmaceutical and biotechnology organizations, we focus on providing customized products and solutions for drug discovery or research projects.
Backgrounds of RFX3
RFX factors play evolutionarily conserved roles in regulating the expression of genes required for the growth, maintenance, and function of cilia. Five RFX factors (RFX1 to RFX5) have been identified in humans and mice. RFX3 is a member of the regulatory factor X gene family that encodes transcription factors with a highly conserved DNA binding domain, and can bind to DNA as both mono- and hetero dimer. RFX3 is first expressed throughout the anterior neural tube and then gradually restricted to specific cell populations. The RFX1, RFX2, and RFX3 genes are expressed at different levels in a wide range of tissues. RFX3 is particularly interesting because it is preferentially expressed in tissues containing ciliated cells, namely the brain, lungs, and testes. RFX3 is specifically expressed in early endocrine cell progenitors as well as in all major endocrine cell lineages in the pancreas of mouse embryos and adults. RFX3 is a transcription factor involved in the control of ciliogenesis, dissection of the RFX3 regulatory cascades in mice could thus contribute to the identification of molecular defects underlying human cilium-related disorders. RFX3 is widely expressed in ciliated cells and is essential for the growth and function of ciliated cells such as embryonic junction cells, cerebral ependymal cells, islet cells, neuron cells, and basal cells. It binds to gene promoters that encode two axon kineto proteins involved in ciliary body movement.
Role of RFX3
- RFX3 regulates two types of genes implicated in cilia biology: genes involved in ciliary assembly (Dync2li1, Foxj1, and Bbs4) and genes involved in ciliary motility (Dnahc11, Dnahc9, and Dnahc5). In addition to the previously known Dync2li1, RFX3 has also been found to regulate a homolog of the human primary ciliary dyskinesia (PCD) associated gene. In mice, RFX3 has been shown to regulate embryonic node and primary cilia growth in the pancreas.
- In addition to regulating cilia, RFX3 also plays an important role in regulating pancreatic endocrine cell differentiation, mature beta cell function, and glucokinase gene expression.
- Rfx3 could perhaps also play a role in the regulation of growth hormone expression.
- RFX3 could transcriptionally activate PROX1, thus facilitating the malignant phenotype of glioma cells.
- FOXJ1 and RFX3 are highly expressed in the small airway epithelium, consistent with the concept that FOXJ1 and RFX3 together may play a pivotal role in maintaining homeostasis of the multi-ciliated cell population in the adult human airway epithelium.
Expression of RFX3 in Diseases
Loss of function of RFX3 resulted in a distorted distribution of neurons, while glial guidepost cell populations did not, both of which were shown to guide the axons of the corpus callosum through the midline. RFX3-deficient mice exhibit ciliary defects in the brain and pancreas, and cilia are characterized by left-right asymmetrical defects, hydrocephalus, agenesis of the corpus callosum, and abnormal thalamocortical tract formation. It also exhibits impaired growth of nodal cilia and consequently leads to embryonic lethality and situs inversus in rare viable adults.
Fig.1 CircRFX3 up-regulates its host gene RFX3 to facilitate tumorigenesis and progression of glioma. (Qian, 2022)
Creative Biolabs identifies, develops, and delivers high-quality biological products and technologies that are essential in a wide range of fields and applications, including drug discovery, diagnostics, and basic research. Our scientists are outstanding, many with years of experience in the pharmaceutical industry and enough professional background knowledge to serve a wide variety of projects. Please feel free to contact us for details.
Reference
- Qian, Y.; et al. CircRFX3 Up-regulates Its Host Gene RFX3 to Facilitate Tumorigenesis and Progression of Glioma. Journal of Molecular Neuroscience. 2022: 1-13.
