These genes are transcription factors containing a bicoid-like homeobox ( Simeone et al., 1992). Otx1 and Otx2 are murine orthologues of the Drosophila orthodenticle ( otd) gene ( Simeone et al., 1992). These results suggest that both Otx genes play important and differing roles in the morphogenesis of the mouse inner ear and the development of its sensory organs. However, within the inner ear, hOtx2 expression failed to rescue the lateral canal and ampulla phenotypes, and only variable rescues were observed in regions where both Otx1 and Otx2 are normally expressed. In mutant mice in which both copies of the Otx1 gene were replaced with a human Otx2 cDNA ( hOtx2 1 / hOtx2 1 ), most of the defects associated with Otx1 −/ − mutants were rescued. In addition, the maculae of the utricle and saccule were partially fused. Histological and in situ hybridization experiments of both Otx1 −/ − and Otx1 −/ − Otx2 +/ − mutants revealed that the lateral crista was absent. Defects in the shape of the saccule and cochlea were variable in Otx1 −/ − mice and were much more severe in an Otx1 −/ − Otx2 +/ − background. Paint-filled membranous labyrinths of Otx1 −/ − mutants showed an absence of the lateral semicircular canal, lateral ampulla, utriculosaccular duct and cochleosaccular duct, and a poorly defined hook (the proximal part) of the cochlea. Ventral to the mid-level of the presumptive utricle, Otx1 and Otx2 were co-expressed, in regions such as the saccule and cochlea. In wild-type inner ears, Otx1, but not Otx2, was expressed in the lateral canal and ampulla, as well as part of the utricle. In this study, we examined, at different developmental stages, the inner ears of mice lacking both Otx1 and Otx2 genes. Previous studies have shown that mice lacking Otx1 display abnormal patterning of the brain, whereas embryos lacking Otx2 develop without heads. In the developing mouse embryo, both Otx genes are expressed in the rostral head region and in certain sense organs such as the inner ear. The Otx1 and Otx2 genes are two murine orthologues of the Orthodenticle ( Otd) gene in Drosophila.
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