Alternative titles; symbols
HGNC Approved Gene Symbol: FZD9
Cytogenetic location: 7q11.23 Genomic coordinates (GRCh38): 7:73,433,778-73,436,120 (from NCBI)
Wang et al. (1997) identified the FZD9 gene, which they called FZD3, by applying CpG island cloning methods to cosmids from the deleted region in patients with Williams syndrome (194050). Sequence comparisons revealed that it encodes a 591-amino acid protein which is a novel member of a 7-transmembrane domain receptor family (see 606143) whose mammalian members are homologous to the Drosophila tissue polarity gene 'frizzled.' The FZD9 gene is expressed predominantly in brain, testis, eye, skeletal muscle, and kidney. 'Frizzled' had been identified as the receptor for the 'wingless' (wg) protein in Drosophila.
Wang et al. (1997) used dosage blotting of DNA from 11 Williams syndrome probands to confirm that the FZD9 gene is located within the Williams syndrome common deletion region at chromosome 7q11.23.
Wang et al. (1997) showed that Drosophila cells, as well as human cells, when transfected with an FZD9 expression construct, bound the wg protein. In mouse, the wg-homologous Wnt1 gene (164820) is involved in early development of a large domain of the central nervous system encompassing much of the midbrain and rostral metencephalon. The potential function of FZD9 in transmitting a Wnt protein signal in the human brain and other tissues suggested to Wang et al. (1997) that heterozygous deletion of the FZD9 gene could contribute to the Williams syndrome phenotype.
Chailangkarn et al. (2016) showed that neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. By analyzing the deletion in an individual with atypical Williams syndrome, Chailangkarn et al. (2016) narrowed this cellular phenotype to a single gene candidate, FZD9. At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation, and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of postmortem layer V/VI cortical neurons.
Zhao et al. (2005) found that Fzd9-null mice had large increases in apoptotic cell death in the developing hippocampal dentate gyrus. Cell death commenced with the onset of dentate gyrus development and persisted into the first postnatal week of life. Heterozygous mice were intermediate between the wildtype and null mice for all developmental neuroanatomic defects. All mice with a mutant allele had a decreased seizure threshold, and Fzd9-null mice had severe deficits on tests of visuospatial learning and memory. Zhao et al. (2005) concluded that FZD9 is critical for hippocampal development and is likely to be a contributing factor to the neurodevelopmental and behavioral phenotype of patients with Williams syndrome.
Chailangkarn, T., Trujillo, C. A., Freitas, B. C., Hrvoj-Mihic, B., Herai, R. H., Yu, D. X., Brown, T. T., Marchetto, M. C., Bardy, C., McHenry, L., Stefanacci, L., Jarvinen, A., and 16 others. A human neurodevelopmental model for Williams syndrome. Nature 536: 338-343, 2016. [PubMed: 27509850] [Full Text: https://doi.org/10.1038/nature19067]
Wang, Y.-K., Samos, C. H., Peoples, R., Perez-Jurado, L. A., Nusse, R., Francke, U. A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23. Hum. Molec. Genet. 6: 465-472, 1997. [PubMed: 9147651] [Full Text: https://doi.org/10.1093/hmg/6.3.465]
Zhao, C., Aviles, C., Abel, R. A., Almli, C. R., McQuillen, P., Pleasure, S. J. Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Development 132: 2917-2927, 2005. [PubMed: 15930120] [Full Text: https://doi.org/10.1242/dev.01871]