Disease relevance of Eya1

• Eya1 heterozygotes show renal abnormalities and a conductive hearing loss similar to BOR syndrome, whereas Eya1 homozygotes lack ears and kidneys due to defective inductive tissue interactions and apoptotic regression of the organ primordia [1].
• We discuss a potential mechanism for the absence of neural precursors in the Eya1-/- inner ears and the primary and secondary mechanisms for the loss of cochleovestibular ganglion cells in the Eya1bor/bor hypomorphic mutant [2].
• The expression of Eya1 in the branchial arch apparatus (namely in the 2nd, 3rd, and 4th branchial clefts and pharyngeal pouches) at embryonic day (E)10.5, can be correlated with the branchial fistulas, sinuses, and cysts but not with the outer and middle ear anomalies [3].

High impact information on Eya1

• Our results indicate that Eya1 controls critical early inductive signalling events involved in ear and kidney formation and integrate Eya1 into the genetic regulatory cascade controlling kidney formation upstream of Gdnf [1].
• Inner ear development in Eya1 homozygotes arrests at the otic vesicle stage and all components of the inner ear and specific cranial sensory ganglia fail to form [1].
• Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia [1].
• Eya1 expression is largely restricted to flexor tendons, while Eya2 is expressed in the extensor tendons and ligaments of the phalangeal elements of the limb [4].
• Later in limb development, Eya1 and Eya2 expression is associated with cell condensations that form different sets of limb tendons [4].

Biological context of Eya1

• Finally, our data suggest that the interaction between Eya1 and Six1 is crucial for the morphogenesis of the cochlea and the posterior ampulla during inner ear development [5].
• Eya1 and Eya2, which are closely related, are extensively expressed in cranial placodes, in the branchial arches and CNS and in complementary or overlapping patterns during organogenesis [6].
• 5. Finally, we found that the surface ectoderm of the 3rd and 4th pharyngeal region show increased cell death at E10.5 in Eya1(-/-) embryos [7].
• Collectively, these data identify Six1 and Eya1 as the first transcriptional complex that is able to reprogram adult slow-twitch oxidative fibers toward a fast-twitch glycolytic phenotype [8].
• The deafness and abnormal behavior were shown to be inherited as an autosomal recessive trait and mapped to mouse chromosome 1 near the position of the Eya1 gene [9].

Anatomical context of Eya1

• Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1 [10].
• These data indicate that Eya1 also regulates mature thyroid gland formation [7].
• Eya1 is also expressed in the 4th pharyngeal region and ultimobranchial bodies [7].
• These results indicate that Eya1 is required for the initiation of thymus and parathyroid gland formation [7].
• In addition, we show that in Eya1(-/-) embryos, the expression of Gcm2 in the 3rd pouch endoderm is undetectable at E10.5, however, the expression of Hox and Pax genes in the pouch endoderm is preserved at E9.5-10 [7].

Other interactions of Eya1

• Finally, our results show that Eya1 and Six1 genetically interact during mammalian kidney development, because most compound heterozygous embryos show hypoplastic kidneys [11].
• We have identified and mapped three members of a new family of vertebrate genes, designated Eya1, Eya2 and Eya3, which share high sequence similarity with the Drosophila eyes absent (eya) gene [6].
• These findings uncover an essential function for Eya 1 as a critical determination factor in acquiring metanephric fate within the intermediate mesoderm and as a key regulator of Gdnf expression during ureteric induction and branching morphogenesis [12].
• The Eya1(bor) mutant hypomorph contains an intracisternal A particle insertion in intron 7 of the Eya1 gene that results in a 50% reduction in wild-type mRNA levels [13].

Analytical, diagnostic and therapeutic context of Eya1

• Quantitative PCR demonstrated that this modifying effect did not result from an increase in wild-type Eya1 mRNA, suggesting Mead1 and Mead2 are interacting directly or indirectly with Eya1 during inner ear development [13].

References