Alternative titles; symbols
HGNC Approved Gene Symbol: EYA2
Cytogenetic location: 20q13.12 Genomic coordinates (GRCh38): 20:46,894,843-47,188,844 (from NCBI)
Abdelhak et al. (1997) identified, by positional cloning, a gene at 8q13.3 that contains mutations in patients with branchiootorenal dysplasia (BOR; 113650). The gene is a human homolog of the Drosophila 'eyes absent' (eya), and was therefore called EYA1 (601653). A highly conserved 271-amino acid C-terminal region was also found in the products of 2 other human genes that were subsequently called EYA2 and EYA3 (601655), demonstrating the existence of a novel gene family. Some of these other members of the EYA gene family may underlie developmental defects, because Abdelhak et al. (1997) demonstrated that all 3 of these genes are expressed in the ninth week of human development.
Gene identification strategies that rely on cross-species comparison are based on the observation that functionally significant regions of the genome are highly conserved during evolution. Banfi et al. (1996) applied the power of Drosophila genetics to the vast resource of human cDNAs represented in the expressed sequence tag (EST) database to identify novel human genes of biologic interest. One human cDNA showing significant homology to the gene causing the Drosophila mutant phenotype 'clift' ('eyes absent') and was reported by Abdelhak et al. (1997) to be the EYA2 gene.
Duncan et al. (1997) found that Eya2 shows a dynamic pattern of expression during mouse development. Its expression was first detected in 8.5-day embryos in the region of head ectoderm fated to become the forebrain. At later stages of development, Eya2 was expressed in the olfactory placode and in a variety of neural crest derivatives. In the eye, expression of Eya2 was first detected after formation of the lens vesicle. At day 17.5, the highest level of Eya2 mRNA was observed in primary lens fibers. Low levels of Eya2 expression were detected in retina, sclera, and cornea. Duncan et al. (1997) stated that, although Eya2 is expressed relatively late in eye development, it belongs to a growing list of factors that may be essential for eye development among metazoan phyla. Like members of the PAX6 gene family (see 607108), 'eyes absent' gene family members were probably first involved in functions not related to vision, with recruitment for visual system formation and function occurring later.
Xu et al. (1997) showed that in the limbs of 10.5-day mouse embryos, Eya1 expression was largely restricted to the flexor tendons, whereas Eya2 was expressed in the extensor tendons and probably also in the ligaments of the phalanges. They demonstrated that the proline/serine/threonine-rich N-terminal regions of the protein products of the Eya1, Eya2, and Eya3 genes have transcriptional activator activity. These results supported a role for the Eya genes in connective tissue patterning in the limbs.
Ridgeway and Skerjanc (2001) induced myogenesis in a mouse pluripotent stem cell line. Myogenesis was associated with increased expression of Pax3 (606597), followed by expression of the transcription factor Six1 (601205), its cofactor Eya2, and the transcription factor Mox1 (600147), prior to the induction of MyoD (159970) and myogenin (159980) expression.
Banfi et al. (1996) mapped the human gene to 20q13.1 using both fluorescence in situ hybridization and radiation hybrid mapping. Zimmerman et al. (1997) mapped the mouse Eya2 gene to chromosome 2 in a region syntenic with human 20q13. Duncan et al. (1997) likewise mapped EYA2 to human 20q13.1 and Eya2 to mouse chromosome 2.
Abdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samson, D., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M., Bitner-Glindzicz, M., Francis, M., Lacombe, D., Vigneron, J., Charachon, R., Boven, K., Bedbeder, P., Van Regemorter, N., Weissenbach, J., Petit, C. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nature Genet. 15: 157-164, 1997. [PubMed: 9020840] [Full Text: https://doi.org/10.1038/ng0297-157]
Banfi, S., Borsani, G., Rossi, E., Bernard, L., Guffanti, A., Rubboli, F., Marchitiello, A., Giglio, S., Coluccia, E., Zollo, M., Zuffardi, O., Ballabio, A. Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching. Nature Genet. 13: 167-174, 1996. [PubMed: 8640222] [Full Text: https://doi.org/10.1038/ng0696-167]
Duncan, M. K., Kos, L., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Tomarev, S. I. Eyes absent: a gene family found in several metazoan phyla. Mammalian Genome 8: 479-485, 1997. Note: Erratum: Mammalian Genome 8: 877 only, 1997. [PubMed: 9195991] [Full Text: https://doi.org/10.1007/s003359900480]
Ridgeway, A. G., Skerjanc, I. S. Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2. J. Biol. Chem. 276: 19033-19039, 2001. [PubMed: 11262400] [Full Text: https://doi.org/10.1074/jbc.M011491200]
Xu, P.-X., Cheng, J., Epstein, J. A., Maas, R. L. Mouse Eya genes are expressed during limb tendon development and encode a transcriptional activation function. Proc. Nat. Acad. Sci. 94: 11974-11979, 1997. [PubMed: 9342347] [Full Text: https://doi.org/10.1073/pnas.94.22.11974]
Zimmerman, J. E., Bui, Q. T., Steingrimsson, E., Nagle, D. L., Fu, W., Genin, A., Spinner, N. B., Copeland, N. G., Jenkins, N. A., Bucan, M., Bonini, N. M. Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene. Genome Res. 7: 128-141, 1997. [PubMed: 9049631] [Full Text: https://doi.org/10.1101/gr.7.2.128]