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Key Event Title
eya1 expression, inhibited
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|GSK3beta inactivation leads to increased mortality||KeyEvent||Cataia Ives (send email)||Open for citation & comment|
|During brain development||High|
Key Event Description
Eya1 is predicted to have protein tyrosine phosphatase activity. Involved in adenohypophysis development; otic vesicle morphogenesis; and otolith development. Predicted to localize to nucleus. Is expressed in several structures, including adenohypophyseal placode; brain; ectoderm; head; and lateral line system. Orthologous to human EYA1 (EYA transcriptional coactivator and phosphatase 1) (ZFIN Gene: Eya1, n.d.).
Eyes absent (Eya) genes regulate organogenesis in both vertebrates and invertebrates. Mutations in human EYA1 cause congenital Branchio-Oto-Renal (BOR) syndrome and hereditary syndromic deafness, while targeted inactivation of murine Eya1 impairs early developmental processes in multiple organs, including ear, kidney and skeletal system (Kozlowski et al., 2005; Xu et al., 2002).
In zebrafish, the eya1 gene is widely expressed in placode-derived sensory organs during embryogenesis. Eya1 function appears to be primarily required for survival of sensory hair cells in the developing ear and lateral line neuromasts (Kozlowski et al., 2005).
How It Is Measured or Detected
Inhibition of expression can be measured with reverse transcription polymerase chain reaction (RT-PCR). This technique is primarily used to measure the amount of specific RNA which is achieved by monitoring the amplification reaction using fluorescence, a technique called real-time PCR or quantitative PCR (qPCR) (Wong & Medrano, 2005). Combined RT-PCR and qPCR are routinely used for analysis of gene expression.
Domain of Applicability
Evidence was provided zebrafish (Kozlowski et al., 2005), Drosophila and vertebrates (Li et al., 2003; Zimmerman et al., 1997), and human (Abdelhak et al., 1997)
Abdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samoson, D., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M., Bitner-Glindzicz, M., & Francis, M. (1997). A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nature Genetics, 15, 157–167. https://doi.org/10.1038/ng0297-157
Kozlowski, D. J., Whitfield, T. T., Hukriede, N. A., Lam, W. K., & Weinberg, E. S. (2005). The zebrafish dog-eared mutation disrupts eya1, a gene required for cell survival and differentiation in the inner ear and lateral line. Developmental Biology, 277(1), 27–41. https://doi.org/10.1016/j.ydbio.2004.08.033
Li, X., Oghi, K. A., Zhang, J., Krones, A., Bush, K. T., Glass, C. K., Nigam, S. K., Aggarwal, A. K., Maas, R., Rose, D. W., & Rosenfeld, M. G. (2003). Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature, 426(6964), 247–254. https://doi.org/10.1038/nature02083
Wong, M. L., & Medrano, J. F. (2005). Real-time PCR for mRNA quantitation. 39(1), 75–85. https://doi.org/10.2144/05391RV01
Xu, P.-X., Weiming, Z., Laclef, C., Maire, P., Maas L., R., Peters, H., & Xin, X. (2002). Eya1is required for the morphogenesis of mammalian thymus, parathyroid and thyroid. Development, 129, 3033–3044.
ZFIN Gene: eya1. (n.d.). Retrieved April 12, 2021, from https://zfin.org/ZDB-GENE-990712-18
Zimmerman, J. E., Bui, Q. T., Kur Steingrimsson, E. [, Nagle, D. L., Fu, W., Genin, A., Spinner, N. B., Copeland, N. G., Jenkins, N. A., Bucan, M., & Bonini, N. M. (1997). Cloning and Characterization of Two Vertebrate Homologs of the Drosophila eyes absent Gene. Development, 124(23), 4819–4826.