Cloning and characterization of two vertebrate homologs of the Drosophila eyes absent gene.

Abstract

The Drosophila eyes absent (eya) gene plays an essential role in the events that lead to proper development of the fly eye and embryo. Here we report the analysis of two human and two mouse homologs of the fly eya gene.Sequence comparison reveals a large domain of -270 amino acids in the carboxyl terminus of the predicted mammalian proteins that shows 53% identity between the fly sequence and all of the vertebrate homologs. This Eya-homology domain is of novel sequence, with no previously identified motifs. RNA hybridization studies indicate that the mouse genes are expressed during embryogenesis and in select tissues of the adult. Both mouse Eya genes are expressed in the eye, suggesting that these genes may function in eye development in vertebrates as eya does in the fly. The mouse Eya2 gene maps to chromosome 2 in the region syntenic with human chromosome 20q13, and the mouse Eya$ gene maps to chromosome 4 in the region syntenic with human chromosome lp36. Our findings support the notion that several families of genes (Pax-6/eyeless, $ix-3/sine oculis, and Eya) play related and critical roles in the eye for both flies and vertebrates.

Xeya3 regulates survival and proliferation of neural progenitor cells within the anterior neural plate of Xenopus embryos

“…So far, temporal and spatial expression of Eya3 during vertebrate embryogenesis has been only reported for the corresponding mouse gene (Xu et al, 1997;Zimmerman et al, 1997). At mouse embryonic stage 8.5-10.5, Eya3 expression was detected within head mesenchyme, branchial arch, and neural tissue, which correspond to similar areas of Xeya3 expression.…”

“…The comparison of mammalian and amphibian EYA3 protein sequences revealed a strong conservation of the functional units of the protein, the N-terminal transactivation domain and the C-terminal phosphatase domain, which are linked by a short more diverged region. In addition, the chromosomal location for the murine Eya3 corresponds to a syntenic region of the human genome (Xu et al, 1997;Zimmerman et al, 1997). Taken together, Eya3 gene expression and function are most likely highly conserved between vertebrates.…”

“…Eya mutations led to an elevated rate of apoptosis in the pool of ommatidial precursor cells, which resulted in a suppression of compound eye development (Bonini et al, 1993Leiserson et al, 1998). In vertebrates, four Eya homologs have been cloned (Duncan et al, 1997;Tomarev, 1997;Zimmerman et al, 1997;Borsani et al, 1999;Fee et al, 2002). Eya1/2 expression in lens and nasal placodes depend on proper Pax6 activity (Xu et al, 1997).…”

Expression of evolutionarily conserved eye specification genes during Drosophila embryogenesis

“…Indeed several orthologs of toy, ey, so, eya, and dac are expressed in mouse and human retinas Grindley et al 1995;Oliver et al 1995;Xu et al 1997;Zimmerman et al 1997;Hammond et al 1998;Caubit et al 1999;Davis et al 1999;Leppert et al 1999;Nishina et al 1999;Terzic and Saraga-Babic 1999;Winchester et al 1999;Davis et al 2001). The expression patterns of these genes suggest that they have been used several times during evolution to specify eye development.…”

A Comparative Study of Eya1 and Eya4 Protein Function and Its Implication in Branchio-oto-renal Syndrome and DFNA10

“…The structure of these proteins as deduced from their cDNA sequences includes a highly conserved 271-amino acid carboxy terminus called the eya-homologous region (eyaHR) and a more divergent proline-serine-threonine (PST)-rich (34%-41%) transactivation domain at the amino terminus (eya variable region, eyaVR) (Zimmerman et al 1997) (Fig. 1).…”