HGNC Approved Gene Symbol: DNAI3Cytogenetic location: 1p22.3 Genomic coordinates (GRCh38): 1:85,062,326-85,133,137 (from NCBI)▼ DescriptionWDR63 is a positiv...
HGNC Approved Gene Symbol: DNAI3
Cytogenetic location: 1p22.3 Genomic coordinates (GRCh38): 1:85,062,326-85,133,137 (from NCBI)
WDR63 is a positive enhancer for osteogenic differentiation of stem cells from apical papilla (SCAPs) (Diao et al., 2015).
▼ Cloning and Expression
Using qualitative PCR, Hofmeister et al. (2018) found that wdr63 was expressed maternally and throughout early developmental stages in zebrafish.
Hofmeister et al. (2018) stated that the WDR63 gene maps to chromosome 1p22.3.
▼ Gene Function
Diao et al. (2015) found that osteogenesis-inducing medium increased trimethylation of lys4 of histone H3 (see 602810) in the WDR63 gene promoter region in human SCAPs. Overexpression of WDR63 enhanced osteogenic differentiation potential of SCAPs, whereas WDR63 knockdown inhibited osteogenic potential and cell proliferation of SCAPs. In vivo transplantation of human SCAPs expressing WDR63 into nude mice led to generation of more bone-like mineralized tissue compared with control cells. Diao et al. (2015) concluded that WDR63 is a positive enhancer for SCAP osteogenic differentiation and suggested that activation of WDR63 signaling may improve tissue regeneration mediated by mesenchymal stem cells of dental origin.
▼ Molecular Genetics
Using array comparative genomic hybridization screening of 66 fetuses with brain malformations and neural tube defects, Hofmeister et al. (2018) identified a heterozygous in-frame deletion in the WDR63 gene in an 18-week-old fetus with occipital encephalocele and inconsistent brain lobulation. The deletion spanned a 15-kb region including exons 14 through 17 of WDR63. Parental DNA was not available to confirm whether the deletion was de novo or inherited. The authors noted that a deletion of similar size had been reported in 2 non-Finnish Europeans without severe pediatric disease. Whole-genome sequencing confirmed the WDR63 deletion in the affected fetus and excluded pathogenic variants in other cilia genes. RT-PCR and Western blot analyses showed that the aberrant WDR63 mRNA was expressed and resulted in a protein lacking the third and fourth WD repeat domains. Experiments in zebrafish (see ANIMAL MODEL) suggested that the WDR63 deletion resulted in expression of a dominant-negative or gain-of-function form of WDR63.
▼ Animal Model
Using CRISPR/Cas9 methods, Hofmeister et al. (2018) created a zebrafish wdr63 mutant mimicking deletion of exons 14 through 17 in human WDR63. Mutant zebrafish embryos showed developmental abnormalities, including body and brain malformations. Overexpression of the aberrant human WDR63 RNA lacking exons 14 through 17 in zebrafish embryos also resulted in similar developmental abnormalities. However, these abnormalities were not observed in the wdr63-knockdown zebrafish, suggesting a gain-of-function or dominant-negative mechanism of the deleted WDR63 variant rather than loss of function.