Vertebrate six genes play major roles in eye, muscle, kidney, and craniofacial development (Kawakami et. al 1996; Brodbeck and Englert , 2004) In vertebrates, Six and Eya genes are also coexpressed with Dachshund (Dach) and Pax genes (including Pax6 but also members of other Pax subfamilies such as Pax2) in various tissues. These include the kidney, somites, retina, and several placodes. Three six genes are expressed in vertebrate PPE, placodes, and/or placode derivatives. However, as reviewed by Brugmann and Moody (2005) the expression patterns across the vertebrates are not identical. The result is not clear whether the differences are the result of true species variation or whether incomplete
descriptions from diverse experimental techniques and different developmental stages make the patterns appear disparate. (Sally, 2007). In general the six1 and six2 are expressed in the PPE, the placodes, the lateral line organs, the muscle precursors, the kidneys, the genitalia, and the limb buds. Six4 is typically expressed in the PPE, the placodes, the muscle precursors, the kidneys, the brain, and the eye. It is important to fully describe the developmental expression patterns of these six genes across all of the animal models and humans to fully understand their roles in placode development and congenital syndromes. (Sally, 2007).
Eya genes encode protein tyrosine phosphatases, which act as transcriptional coactivators of Six genes (Due to gene duplication, there are four Eya genes in vertebrates, whereas invertebrates have only a single Eya gene All Eya genes except Eya3 are widely expressed in cranial placodes, with each placode expressing at least one Eya gene, although the distribution of the different paralogues among placodes differs for different species. (Schlosser, 2006)
Eya1 and Six1 were both identified as genes underlying particular forms of inherited deafness in humans known as branchio-otic (BO) or branchio-oto-renal (BOR) syndrome, which are associated with branchial or branchial and renal defects, respectively.
In Drosophila, it has first been shown that sine oculis and eyes absent-homologues of the vertebrate Six1/2 and Eya genes, respectively-form a regulatory network essential for compound eye development together with the nuclear protein dachshund and the Pax6 homologue eyeless. compound eye development. Conversely, these genes synergize in promoting ectopic eye formation after
misexpression and Niimi et al., 1999 T. Niimi, M. Seimiya, U. Kloter, S. Flister and W.J. Gehring, Direct regulatory interaction of the eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila, Development 126 (1999), pp. 2253-2260. View Record in Scopus | Cited By in Scopus (68). Because the same set of genes is also coexpressed elsewhere in the embryo, a similar regulatory network may operate in other developmental contexts, although this has not been rigorously analyzed.
Furthermore, some regulatory intera